New Grant Funding

I'm pleased to announce that I have been awarded an internal Academic Health Center Seed Grant for a new project titled "Mechanism of Action of RITA, a Small Molecule for MLL Leukemias" for 2011–2012. Although the grant is small, $25,000, it will be a big help in getting this new project off the ground. This is a project that I have recently begun with Professor John Kersey, the Founding Director of the Masonic Cancer Center, as well as my medicinal chemistry colleague, Dan Harki. The structure of RITA (NSC 652287, below) is rather simple, but its anticancer activity is extremely intriguing and has provided us with many avenues to study.

Congratulations to Will Fiers

This past Thursday, July 28, Will Fiers successfully passed his Preliminary Oral Examination! Will is a second-year graduate student in the lab, and he did an exceptional job in defending his written proposal, "Synthesis and Biological Activity of Constrained 7-Oxozeaenol Derivatives." He is now officially a Ph.D. candidate. Congratulations are in order to Will for passing this milestone!

Seminars This Week

Today is the day that I'm proud to be hosting Scott Snyder from Columbia University for his seminar at noon titled "Lessons in Chemoselectivity: Total Synthesis of Polyphenolic Natural Products" in 7-135 Weaver-Densford Hall. Scott and I overlapped at Scripps for a couple years, so it will be great to hear about the success of his independent research program at Columbia.

Alison Frontier from the University of Rochester will then be on campus this Wednesday and Thursday for the latest Abbott Workshop Series in Synthetic Organic and Medicinal Chemistry hosted by the Department of Chemistry. Her seminar, "New Twists in Nazarov Cyclization Chemistry," will be on Wednesday at 4:15 pm in 331 Smith Hall. The workshop discussion will be held on Thursday, July 14 at 10:00 am in 114 Science Teaching & Student Services. This will be followed by a pizza lunch, and the Fecik group meets with Alison from 1:30-2:15 pm.

Seminars Next Week

There are three seminars of interest taking place next week. On Monday, June 27, Dr. Henry Wong will present his talk "Adnectins: A Novel Class of Targeted Protein Therapeutic" in 7-135 Weaver-Densford Hall at 11:00. Dr. Wong is a candidate for the Pharmacologist position in ITDD.

As part of the Medicinal Chemistry Seminar Series, Kathryn Nelson, a third-year graduate student in Courtney Aldrich's lab, will present her research seminar titled "Total Synthesis and Biological Evaluation of the Siderophore Acinetobactin and the Structurally Related Natural Product (+)-Transvalencin Z" on Tuesday, June 28 in 7-135 Weaver-Densford Hall at 11:30. Lunch will be provided, but you will need to bring your own drink.


Lastly, the Microbiology, Immunology, and Cancer Biology (MICaB) program will be hosting Dr. Bill Phelps as part of their Career Development Seminar Series. Bill is a Program Director at the American Cancer Society (ACS), and he leads the ACS study section on Cancer Drug Discovery on which I have served. He will be speaking at 12:00 noon on Thursday, June 30 in 450 MCRB, and the title of his talk is "Perspectives on Cancer Research from a Career Path in Academia, Government, Industry and a Private Foundation" and "How The ACS Supports Cancer Research." Bill is a Minnesota alumnus and he received his Ph.D. in Microbiology in 1985 at Minnesota. Prior to his appointment at ACS in 2001, he was a postdoc at NCI and a scientist at Burroughs-Wellcome/GlaxoWellcome/GlaxoSmithKline for several years. Bill's a great person, and he will provide a fascinating insight to cancer research and grant funding. Lunch will be provided, but you must RSVP for lunch here by Wednesday, June 29 at noon.

Fall Chemical Biology Interest Group Meetings Announced, Group Meeting Updates

The Fall 2011 meeting schedule for the monthly Chemical Biology Interest Group has been announced. The calendar has been updated with the following dates:


Thursday, August 18: Finzel and Xing groups
Thursday, September 15: Wagner and Aldrich groups
Thursday, October 20: Distefano and Amin groups
Thursday, November 17: Harki and Fecik groups


All meetings begin at 6:30 pm in 7-135 Weaver-Densford Hall, and pizza will be served.


Details for the summer Fecik-Georg joint group meetings have been updated through August (see calendar). Due to various out of town commitments, including the Fall National American Chemical Society Meeting, group meetings for August have been canceled. Meetings will resume again in September.

Chemistry Biology Interface Training Grant Symposium Recap

Chemistry-Biology Interface Training Grant Symposium

Wednesday, May 25, 2011

University of Minnesota, Mayo Auditorium

The Chemistry Biology Interface Training Grant Symposium is held annually as part of the University of Minnesota's NIH-funded grant of the same name. The day's events included a midday poster session and mix of external and internal speakers, including a grant trainee.


Mark Distefano opened the morning with introductory remarks before the first speaker, Rami Hannoush from Genentech. His talk, "Chemical Probes for Inhibiting Wnt Signaling and Visualizing Protein Fatty Acylation," was focused on two subjects. The first part was centered around his work on studying protein-protein interactions and assembly of Wnt signaling complexes in order to discover drugs that interrupt Wnt signaling for cancer. Switching gears, Rami then presented research on the use of fatty acid analogs for imaging protein modification by lipids. This was a fantastic talk that demonstrated the power of new methods for the design of biological probes useful in drug discovery.

Rami Hannoush (Genentech) with Professor Yusuf Abul-Hajj.

Click picture to see more photos from the symposium.

Next up was Leah Randles, a fifth year graduate student and 2007–2009 grant trainee from Kylie Walters' lab, with her talk "Regulation of the Proteasomal Ubiquitin Receptor Rpn13." She presented a lot of intriguing work on using various NMR solution structures to study the role of hPLIC2 as a negative regulator of Rpn13 activity. Leah fielded a lot of questions and spoke with many people about her findings after the talk.


Over 30 posters were presented over lunch in the lobby of Mayo Auditorium. There were a lot of outstanding posters, and much discussion ensued amongst the participants during the 90 minute session.

Intense studying at the poster session.

Click picture to see more photos from the symposium.

Following lunch and the poster session was Professor Adrian Hegeman from the Department of Horticultural Sciences at Minnesota with a presentation entitled "Plant Metabolomics Methodology: Using in Vivo Stable-Isotope Labeling for Elemental Composition Assignments." I was unfamiliar with his work, so this talk was a fascinating insight as to how plant metabolomics can be used to study plant behavior and production of nutrients and responses to stress.


Joseph Beckman from Oregon State University then provided a thought-provoking talk on peroxynitrite, superoxide dismutase (SOD), and amyotrophic lateral sclerosis (ALS) titled "Oxidative Stress and the Chemical Biology of Neurodegeneration: Did Free Radicals Kill Lou Gehrig?" Much of the talk focused on post-translational modification of proteins by nitration of tyrosine residues and evidence that mutations to SOD are involved in ALS. The role of nitration in the regulation of protein function, particularly Hsp90, was also presented.


I unfortunately had to miss the final lecture of day delivered by Leona Samson from MIT on "Complex Biological Responses to DNA Damage." The entire event was a wonderful learning experience, and the organizing committee did an exceptional job of delivering a fantastic program that reflects the diversity and importance of chemical biology research.

Seminars Next Week

It's great that seminars continue here throughout the summer, and three have been announced for next week. On Monday, June 20 Lih-Wen Deng from the National University of Singapore we present "Function of Mixed Lineage Leukaemia 5 in Cell Cycle Regulation" as part of the Chemical Biology Colloquium series. The talk will in 3-100 Mayo Auditorium at 12:15 pm, and pizza and beverages will be served.

The summer Medicinal Chemistry seminar series will kick off on Tuesday, June 21 with a graduate student presentation from Amit Gangar (Wagner lab) at 11:30 am in 7-135 Weaver–Densford Hall. Amit's talk is titled "Design and Development of Bispecific Chemically Self-Assembled Nanostructures for Anti-Cancer Drug Delivery." Lunch will be provided, but BYOB (bring your own beverage).


A special seminar will be given on Wednesday, June 22 at 9 am in 7-135 Weaver–Densford Hall by Dr. Krishnan Subbiah titled "Targeted Oncology Therapeutics: In Vivo Pharmacology." Dr. Subbiah is a candidate for the Pharmacologist position in the Institute for Therapeutics Discovery and Development.

It will be busy seminar week, but I'll see everyone there!

Jesse Ventura's Prozac Ignorance

My daily break from all things serious is listening to "Darkness on the Edge of Town", the self-proclaimed "best in paranormal talk radio" show on 100.3 FM KTLK. Their guest last Monday was none other than former Minnesota Governor Jesse "The Body" Ventura, who is out promoting his latest book on conspiracy theories. Among the wacky ideas he was peddling was this doozy about fluoride in drinking water:


"Do you want to know who the first person was to put fluoride in water? The Nazis. Now I'll tell you why. Do you know what fluoride is the 90% main ingredient to? Prozac. So when you're drinking fluoride water you're essentially drinking liquid Prozac. That's called the dumbing down of society. Think about that. Yet they force it upon us and they tell us it's for our teeth."


You can download the June 6, 2011 episode from the KTLK website, and this comment was made at the 31:47 mark.


It's really disturbing that anyone would believe this, and even more disturbing that this type of sheer ignorance is being promoted by our former Governor. First, I'm not aware of any credible data that fluoride in drinking water has any type of mood-elevating or anti-depressant activity akin to Prozac. Second, there is no evidence that fluoride is released from Prozac when it is metabolized in humans. Lastly, fluorine is not the "90% main ingredient" of Prozac. Below is the chemical structure of Prozac (aka fluoxetine) and its elemental analysis showing that fluorine comprises approximately 18% of its molecular weight.

I'll let you draw your own conclusions about Governor Ventura's belief that this is a Nazi-inspired plot to control the entire United States population. 

Amber Onorato Invited to Natural Products Gordon Conference as Discussion Leader

Congratulations to Amber Onorato, a postdoc, on being invited to serve as Discussion Leader at the Gordon Research Conference on Natural Products this year! She was recently invited by the Program Chair, Karl Hansen (Amgen), to be Discussion Leader for one of the sessions on Pharmaceutical Process Chemistry. This year, the Gordon Conference will be held at Bryant University in Smithfield, RI from July 24–29. The Natural Products Gordon Conference is one of the premier international meetings in the field, and it's always an amazing experience to attend. It's perhaps my most favorite meeting, but unfortunately I cannot attend this year due to the expected arrival of a daughter the summer. Amber presented a poster at last year's meeting, and it's great that she has the opportunity to attend again as a Discussion Leader.

David Sherman - Abbott Workshop Recap

Professor David Sherman, University of Michigan

Abbott Workshop in Synthetic Organic Medicinal Chemistry

Friday, May 20 and Saturday, May 21, 2011

I had the distinct privilege of hosting my friend and collaborator, Professor David Sherman, from the University of Michigan on May 20 and 21 for the Abbott Workshop in Synthetic Organic Medicinal Chemistry in the Department of Chemistry. This was David's first seminar presentation at Minnesota since he left here for Michigan in 2003. The Abbott Workshop is a fantastic seminar series since it provides graduate students with extensive opportunities for interacting with prominent speakers in small groups and in a discussion-based workshop session.

David address the audience during his Friday afternoon seminar.

David with former postdocs Christine Salomon and Courtney Aldrich.

Following the usual day of visiting with chemistry faculty, lunch with students, and participation in the weekly Synthesis Literature Meeting, David presented his Friday afternoon seminar, "Novel Drug Leads from Natural Products and Their Derivation from Microbial and Biosynthetic Diversity." He began with an overview of the changes that have taken place in studying bacterial genetics and secondary metabolism and a description of his discovery efforts in Costa Rica as a teaser for the Saturday workshop. David then led the audience through some of his work on polyketide biosynthesis in three parts. First was a project-spanning walk through his ground-breaking work on pikromycin biosynthesis, subtitled "Interrogating Molecular Specificity in Modular PKSs." Having collaborated with David on much of this research, it was fascinating to realize how much has been accomplished in the study of macrolide antibiotics, yet also exciting at the opportunities that remain. The second part, "Biosynthetic P450s as a Tool for C–H Bond Activation," described his work in using PikC, a P450 tailoring enzyme in pikromycin biosynthesis, for the oxidation of a remarkable variety of non-natural substrates. Finally, new research that has been accepted for publication in Nature Chemistry on the unusual biosynthesis of tirandamycins was presented to close the talk.

Friday dinner at Sen Yai Sen Lek. L–r: Christine Salomon, Andy Harned, Tom Hoye, Chris Douglas, David Sherman.

Christine Salomon and Courtney Aldrich, both former postdocs of David's, and I chatted with David for a while after his talk, and I briefly showed him around our new labs in the 717 Delaware Building before heading to dinner at Sen Yai Sen Lek. David, Christine, Tom Hoye, Andy Harned, Chris Douglas, and I shared some delightful Thai food and a lot of laughs over David's stories from collecting expeditions in Costa Rica.

David presents his Saturday morning workshop discussion.

I met David for breakfast at Starbuck's on Saturday morning, and this offered us our first opportunity to catch up with each other and discuss some future project ideas. Beginning at 10 am, David led the packed room in a two and a half hour discussion about natural products discovery and his International Cooperative Biodiversity Group, which encompasses synergistic collaborations with Giselle Tamayo (INBio, Costa Rica), Jon Clardy (Harvard Medical School), Phil Crews (UC-Santa Cruz), Verenium (San Diego), the Joint Genome Institute (Berkeley), and Eisai. As you can imagine, the scope and objectives of the group are huge and ambitious. His informal presentation led into discussions about beetles and bioenergy production, marine sample collecting, political issues, and the study of symbiont biosynthetic pathways, including that of ET-743 (aka ecteinascidin 743, trabectedin, Yondelis). The pizza lunch arrived too quickly, and everyone seemed to enjoy the unique discussion. David's afternoon was spent meeting individually with the Fecik, Hoye, Harned, and Douglas research groups, and his visit ended with dinner Saturday evening with a group of students.


Overall, the two days with David were invigorating and stimulating, and his unique perspectives on modern natural products research were beneficial to all.


The next Abbott Workshop will be July 13 and 14, when the Department of Chemistry will be hosting Professor Alison Frontier (University of Rochester).

Pharma Strategy Clinic Seminar: Pharmaceutical Innovation at a Crossroads with Kenneth Kaitin

As part of the Pharma Strategy Clinic Seminar Series sponsored by the Office of the Vice President for Research (OVPR), Professor Kenneth Kaitin from Tufts University will present a seminar titled "Pharmaceutical Innovation at a Crossroads: The New Face of Pharma R&D" on Wednesday, June 8 at 11:30 am in 2-530 Moos Tower. Ken is widely recognized for his expertise in the landscape of drug development, and his talk will focus on academic-industrial drug discovery partnerships. A light lunch will be served before the seminar, and no RSVP is required. More information about Ken can be at found at the OVPR Research News Online website.

Congratulations to the Class of 2011

Commencement was held on May 7 for the Pharm.D., Ph.D., and M.S. graduates in the College of Pharmacy. This was the first year that the Ph.D. and M.S. graduates received their degrees alongside the Pharm.D. graduates. It was also the first time that the ceremony was held at Ted Mann Concert Hall, which provided a much more intimate setting than Northrup Auditorium in the past. Congratulations are in order for all the graduates for their success and years of hard work in achieving such as significant accomplishment. As the Pharm.D. Class Advisor in the Twin Cities, I am especially proud of the class and it was fun to work with them during the last four years.

The Pharm.D. Class of 2011

Graduate festivities were kicked off the night before graduation on Friday, May 6 with the Pre-Commencement Celebration and Awards ceremony at the DQ Club Room in TCF Bank Stadium. It was a fun time to visit with the students and talk with them about their future plans. The Pharm.D. selected their Preceptors of the Year, and they were recognized for provided exceptional experiences for students during their clinical rotations. The main reason for the celebration was formal recognition of a variety of awards given to students for excellence and achievement in many professional activities. I was given two minutes to address the class, and the focus of my comments was that the Pharm.D. degree provides a strong scientific foundation for success for any future professional endeavor in patient care and drug research. It was also the first time that I've had a speech piped into bathrooms!


Prior to Commencement, faculty were invited to a brunch at the Hubert H. Humphrey Center to recognize teaching awards. I was honored to be selected Professor of the Semester for both the Twin Cities and Duluth campuses for Fall 2010 from the Class of 2013.

Faculty proceed towards the stage of Ted Mann Concert Hall

Introductory remarks from Henning Schroeder, Vice Provost and Dean of the Graduate School

Ted Mann was a beautiful site for Commencement along the Mississippi River on the West Bank of campus, and we were fortunate to have a gorgeous spring day. Following the usual introductory remarks from University officials, the Class Speakers from the Duluth campus, Benjamin Aronson, and the Twin Cities campus, Matt Hammer, were introduced for their addresses to the class. Ben's speech incorporated a rap song, which was certainly unique. The Teachers of the Class, Mike Swanoski (Duluth) and Jeannine Conway (Twin Cities), also addressed the class with some inspiring comments. United States Senator Amy Klobuchar was the invited Commencement Speaker, and her 20 minute talk about growing up in Minnesota, her experiences in Washington, DC, and the changes taking place in our health care systems was fitting for the occasion. Senator Klobuchar was both witty and charming in her delivery, and it's easy to see why she's a popular figure in Minnesota and Washington, DC. The funniest part of her talk was her story about nearly walking out before President Bill Clinton at an event during her days as an intern. You can listen to Senator Klobuchar's speech here.

Senator Amy Klobuchar address the Pharm.D. Class of 2011

Conferral of degrees

Our new Associate Dean for Graduate Education, Esam El-Fakahany, presented 13 students with their Ph.D. and M.S. degrees from all departments in the College. I had the task of presenting all 160-odd Pharm.D. graduates, and fortunately I didn't lose my place on the list as I was reading the names. Following recitation of the Professional Oath of a Pharmacist by the class, Dean Marilyn Speedie provided the closing remarks. The Metropolitan Men's Chorus closed the event with their rendition of "Hail! Minnesota" and an Irish Blessing. Their improvised verse in "Hail! Minnesota" is quite funny and always brings down the house. Commencement was a wonderful event this year, and I offer my sincere congratulations to the class.

Metropolitan Men's Chorus sings "Hail! Minnesota"

All photos are from the College of Pharmacy, and additional photos can be viewed by clicking on any of the pictures above or by clicking here.

Neal Rosen Seminar Recap

Neal Rosen, Enid A. Haupt Chair in Medical Oncology at the Memorial Sloan–Kettering Cancer Center, visited Minnesota on May 18 to present the keynote lecture at the Masonic Cancer Center Research Symposium in the Great Hall of Coffman Memorial Union. Due to conflicting meetings, I could not attend the rest of the Symposium, so my comments are limited to Dr. Rosen's talk. Doug Yee, Director of the Masonic Cancer Center and a former postdoc in Neal's lab, gave him a warm introduction to the assembled crowd.


The title of Neal's presentation was "Feedback Regulation of PI3K-Signaling Pathways–Biologic and Therapeutic Implications." The main theme of the talk was what he calls adaptive resistance of cancers to oncoprotein inhibition by small molecule drugs. He presented data with MAPK and AKT kinase inhibitors to show that inhibition of these oncoproteins relieves upstream feedback inhibition and can attenuate the effects of therapy resulting in oncogene addition - sustained negative feedback throughout the signaling network.

Dr. Rosen takes a question from the crowd

A couple points about the choice of drugs to study were made. First, Neal made the point that drugs are the best way to understand adaption to pathways since this can't be done with siRNA. Second, allosteric kinase inhibitors are preferred, presumably due to issues related to target selectivity. He also related key reasons why effects of a drug can be limited in humans: poor patient selection, suboptimal drug, inadequate pathway inhibition, and adaptive resistance.


Neal closed the talk with a proposal for the design of clinical experiments with oncoprotein inhibitors. A four-step treatment process was proposed with the goal of maximizing tumor cell death:
1. Biopsy the patient's tumor and determine the driver mutation.
2. Treat the patient with an inhibitor of the driver protein at the maximal tolerated dose for x hours.
3. Re-biopsy the tumor and determine its mechanism of adaptation
4. Treat the patient with the driver inhibitor and an inhibitor of the putative dominant driver of the adaption.


This was an informative presentation that captured the interest of both basic and clinical scientists in the audience. Although most of the data was published, Neal put forth some provocative ideas that are sure to spark discussion within the oncology community.

Symposia And Seminars This Week

Despite the Spring semester being over, this is another busy week on the seminar front. Tomorrow, Wednesday, May 24th, brings us the annual Chemical Biology Interface Training Grant Symposium in Mayo Auditorium. Following opening remarks, the talks begin at 10:00; here is the complete schedule, and the full details can be found here:
10:00 - Rami Hannoush (Genentech)
11:15 - Leah Randles (University of Minnesota)
12:00 - Lunch and Poster Session
1:30 - Adrian Hegeman (University of Minnesota)
2:30 - Joseph Beckman (Oregon State University)
3:40 - Leona Samson (Massachusetts Institute of Technology)

An impressive list of speakers is then scheduled for Thursday, May 26 for The Lee W. Wattenberg Symposium on Cancer Chemoprevention: Past Achievements, Future Strategies. This event to honor Dr. Wattenberg with the AACR Award for Lifetime Achievement in Cancer Prevention Research is co-sponsored by the American Association for Cancer Research (AACR) and the National Cancer Institute (NCI), and will be held from 10:30–3:00 in the Al Johnson Great Room at McNamara Alumni Center. Click here to read a nice summary of Dr. Wattenberg's groundbreaking research for which he is being honored. Here is the schedule for the morning and afternoon sessions:


10:30–12:15
Margaret Foti (AACR) - Cancer Prevention and Its Vital Role in the Conquest of Cancer
Lee W. Wattenberg (University of Minnesota) - Late-stage Inhibition and other Strategies for Prevention of Neoplasia
Stephen S. Hecht (University of Minnesota) - Extending the Pioneering Work of Lee Wattenberg on Chemoprevention of Lung Carcinogenesis
Waun Ki Hong (University of Texas) - Personalized Approach in Lung Cancer: Reverse Migration Strategy


1:00–3:00
Allan Conney (Rutgers University) - Person-to-Person Differences in Drug Metabolism: Importance for Cancer Chemoprevention
Frank G. Ondrey (University of Minnesota) - PPAR Gamma Activation as a Strategy in Aerodigestive Cancer Prevention: A Surgeon's Perspective
Stephen Lam (British Columbia Cancer Agency) - A Pathway Approach to Lung Cancer Chemoprevention in High-risk Smokers
Frank L. Meyskens, Jr. (University of California Irvine) - Rethinking the Runway for Successful Development of Chemoprevention for the Clinic: Hard Lessons Learned
Eva Szabo (NCI) - From Mouse to Man: The Budesonide Story and What it Has Taught Us

Lastly, we are fortunate to have back at Minnesota Gerhard Höfle from the Helmholtz Center for Infection Research on Friday, May 27. He will be presenting his seminar, Development of Epothilone and Tubulin Inhibitors as Anticancer Agents, at 3:00 in Room 105, 717 Delaware. Dr. Höfle is a world-renowned natural products chemist, and he has discovered dozens of bioactive natural products, including the epothilones and tubulysins, from myxobacteria. He gave the keynote lecture in 2007 at the Engebretson Symposium in Drug Discovery and Development in Natural Products, and his lecture should again be instructive and insightful.

Gerhard Höfle and I at the Engebretson Symposium in Minneapolis on November 12, 2007

LesFest Recap, Part 2

2011 Lester A. Mitscher Symposium

May 12–14, 2011

Lawrence, KS

University of Kansas, Pharmacy Building and Oread Hotel

Celebrating Professor Mitscher’s 80th birthday and his contributions to the field of medicinal chemistry and to the University of Kansas

Part 1 of my LesFest recap can be read here.

The symposium to honor Les was held on Friday, May 13th in the beautiful new Pharmacy Building on West Campus. Dan Flynn chaired the morning session, which featured talks by me, Steven Djuric, and Dale Boger. Barbara Timmerman (University Distinguished Professor and Chair of the Department of Medicinal Chemistry), Ken Audus (Dean, School of Pharmacy), and Bernadette Gray-Little (Chancellor, University of Kansas) opened the proceedings with some warm, kind words about Les and his lasting contributions to the Department, School of Pharmacy, and University.

The Mitscher Symposium speakers (l–r): Dale Boger, Robert Fecik, Ashok Bhatia, George Ellestad, Les Mitscher, Dan Flynn, Gunda Georg, and Stevan Djuric.

Click on the picture to see more photos from the Mitscher Symposium.

I had the challenging task of giving the first scientific talk of the day, and chose to start my talk with some person reflections about Les and my time at Kansas. I’ll share some of those comments at the end of this post. I was feeling a bit under the weather and my voice was rough, but I thought the talk about some aspects our tubulysin project went very well. The feedback I received was overwhelmingly positive, and I got a lot of excellent suggestions and ideas from members of the audience.

Stevan Djuric from Abbott was up next, and he gave a very interesting talk on new chemistry technologies and methods he and his team have developed. It was a very insightful and thought-provoking presentation about the technological innovations taking place in industry. Stevan is a close friend of Les’ from their many years working together during Les’ consulting.

My postdoc mentor, Dale Boger (Scripps), closed out the morning session with great talk about the amazing chemistry developed for the total synthesis of Vinca alkaloids. This was an updated version of the talk he gave at last year’s National Medicinal Chemistry Symposium, and it included some new vinblastine analogs and biological data. It’s incredible work, and Dale always gives a fabulous presentation. Les hired Dale at Kansas while he was Chair, and Dale recounted some outstanding advice he received from Les while a junior faculty member.

Over lunch I had a enjoyable time catching up with my old friend Tim Caldwell, a former student of Gary Grunewald’s who is now at Deciphera Pharmaceuticals. The time passed quickly, and I had to get back to prepare for the afternoon session.

I had the pleasure of introducing the afternoon speakers, beginning with Dan Flynn, President and CEO of Deciphera Pharmaceuticals, who received his Ph.D. with Les in 1981. Dan’s had an amazing career in pharma, so it’s no surprise that he’s had incredible success with Deciphera, the company he founded in 2003. He presented the ingenious “switch control inhibitor” approach towards the design of kinase inhibitors, which has resulted in an Abl kinase inhibitor that entered a Phase I clinical trial last year. This is amazing work, and Dan had presented a version of this talk a couple months ago here at Minnesota.

George Ellestad was hired by Les at Lederle in 1964, and this launched his remarkable, nearly 40-year career at Lederle and Wyeth. He conducted seminal natural products chemistry through his career, including contributions that led to the development of tigecycline, a glycylcycline tetracycline antibiotic. George is also a Member of the American Chemical Society Division of Medicinal Chemistry Hall of Fame, in part for his ground-breaking work on the identification and mechanism of action of calicheamicin, an enediyne antitumor antibiotic. This lead to the development of Mylotarg, a calicheamicin–antibody conjugate, that was the first drug–antibody conjugate approved for clinical use. Since 2005 George has been an Adjunct Senior Research Chemist at Columbia University. In his talk, George gave a fascinating recount of the structure elucidation, mechanistic studies, and bioconjugate chemistry that ultimately led to the discovery of Mylotarg.

Ashok Bhatia from the Process R&D group at Abbott was up next. Ashok also received his Ph.D. with Les in 1981, and has had a very successful and productive career at Bouroughs–Wellcome and Abbott. Today he spoke about the development of a couple pilot-scale routes to an H3-receptor antagonist, which included some interesting metal-catalyzed cross-coupling chemistry. Process chemistry talks are always fascinating to me, and Ashok’s presentation was extremely insightful.

Although the end of a long day was approaching, it’s always a pleasure to hear about the latest work from Gunda Georg, Chair of Medicinal Chemistry at Minnesota. Les hired Gunda at Kansas in 1984, and we were fortunate to lure her here to Minnesota in 2007. Gunda also relayed advice she received from Les early in her career prior to delving into a two-part talk. The first part described the discovery of minnelide, a triptolide prodrug that is scheduled to begin a Phase I clinical trial later this year. In the second half, she presented enaminone methodology that been used for the total synthesis of tyloindicine alkaloids and analogs. Her talk ended a fantastic day of talks, and all presentations were very well-received.

At the conclusion of the talks, a poster session was held in the lobby of the Pharmacy Building. Twenty posters were presented, including ones by my students, Mike Peterson, Will Fiers, and Yang Li. The poster session was cut a little bit short due to the length of the oral presentations, but everyone stuck around to visit the posters for a while.

The festivities then moved over to the Oread Hotel for a banquet dinner. The food was among the best I’ve ever had at a banquet, and a social hour provided ample time to meet many people I hadn’t had a chance to visit with up to this point. After dinner, the highlight of the evening was a slide show by Les, during which he recounted many stories about his family, research, friends, and travel throughout his career. It was emotional at times, especially when talking about family, and the presentation was both heart-warming and inspirational. This was followed by some words from Les’ sons who talked about their views in growing up in the Mitscher household and how much Dad and Mom mean to them. It was a fitting end to an wonderful evening, and it was hard not to be overwhelmed by the outpouring of love and affection shown to Les by everyone. After everyone had left, my students and I visited with several of the KU students for a while before calling it a night.

Robert Fecik, Les Mitscher, and Pratik Devasthale at the Mitscher house.

Click on the picture to see more photos from the Mitscher Symposium.

The next day, Saturday, Les and his wife, Betty, hosted the out of town guests at their home for an informal open house around noon. It was a relaxed atmosphere, and it gave everyone the opportunity to visit with each other once more before departing Lawrence. There were simply too many great people I met and caught up with to mention everyone by name, but one personal highlight was finally meeting Pratik Devasthale. Pratik received his Ph.D. with Les, and I took over his thesis work on quinolone antimicrobials when I joined Les’ group. He has since gone on to do great work at BMS, most notably the discovery of muraglitazar (Pargluva), a dual alpha/gamma-PPAR agonist for type 2 diabetes that was submitted for marketing approval to the FDA but was ultimately never approved for a variety of factors. After giving my thanks and best wishes to Les and Betty, I picked up my students at the hotel and we hit the road for a rainy drive back to Minneapolis.

I know that everyone has the most profound respect and admiration for their graduate advisor, but my feelings for Les extend far beyond this. Each person that I spoke with over these three days had their own stories of Les’ generosity and thoughtful advice that further cemented Les’ reputation as a great man and scientist. I’ll forever be grateful for all that he taught me; things that still inspire and motivate me today.

Fecik–Harki Labs St. Paul Saints Tailgating Game Tomorrow!

Tomorrow evening is the group's night out tailgating with the Harki group before the baseball game between the St. Paul Saints and the Fort Worth Cats at Midway Stadium. It's also Night at the Museum(s)...of Minnesota at game, whatever that means. Game time is 7:05 pm, but we will be set up in the tailgating lot shortly after 4. Although there's a 30% chance of rain early in the day, it should be sunny and partly cloudy around game time. There will be plenty of drinks and food before the game, including brats, hot dogs, hamburgers, fruit, vegetables, Smores, and other assorted treats. It should be a fun night, and I'm looking forward to seeing everyone there!

Summer Seminar Scheduled Announced, Scott Synder (Columbia University) Confirmed

The Department of Medicinal Chemistry released its Summer 2011 seminar program today, which runs from June 21 to August 2. The summer talks are reserved for third year graduate students to present their research seminar. There was one open slot for an external speaker, and I'm pleased to be hosting Assistant Professor Scott Snyder from Columbia University on Tuesday, July 12. Scott is a friend since the time we overlapped at Scripps where he received his Ph.D. with K.C. Nicolaou in 2004. He's off to a fantastic start in his independent career at Columbia, which he began in 2006. Scott gave a great, inspiring talk at the Natural Products Gordon Conference a couple years ago, so this will be a super seminar. The title of Scott's seminar is "Lessons in Chemoselectivity: Total Synthesis of Polyphenolic Natural Products."

Scott Snyder

Here's the entire summer seminar schedule. All talks are in 7-135 WDH; lunch will be served at 11:30 (bring your own drinks), and the seminars begin at noon.


June 21 - Amit Gangar (Wagner lab): Design and Development of Bispecific Chemically Self-Assembled Nanostructures for Anti-Cancer Drug Delivery


June 28 - Kathryn Nelson (Aldrich lab): Total Synthesis and Biological Evaluation of the Siderophore Acinetobactin and the Structurally Related Natural Product (+)-Transvalencin Z


July 5 - Adwait Ranade (Georg lab): Syntheses of a 2,3-Dihydropyridone Library and Epothilone Photoaffinity Probes


July 12 - Scott Snyder (Columbia University): Lesson in Chemoselectivity: Total Synthesis of Polyphenolic Natural Products


July 19 - Srikanth Kotapati (Tretyakova lab): Urinary Biomarkers of Human Exposure to 1,3-Butadiene (BD) and Influence of BD–DNA


July 26 - Xia Zhang (Amin lab): Experimental and Computational Methods for Identification of Novel Fungal Histone Acetyltransferase Rtt109 Inhibitors


August 2 - Martin Phillips (Peterson lab): The Chemistry of Bioactivated Electrophilic Intermediates of Furan

Seminars This Week

There’s a couple events of interest this week. The 2011 Research Symposium of the Masonic Cancer Center will be held from 9–3:30 this Wednesday, May 18 at the Great Hall in Coffman Memorial Union. This annual symposium highlights the breadth of great work going on here at the cancer center, and this year is no exception. Neal Rosen from the Memorial Sloan-Kettering Cancer Center kicks things off with the keynote address, "Oncoprotein-feedback Inhibition of Signaling—Biologic and Therapeutic Implications", at 9:30, followed by a poster session and lunch. The afternoon session features researchers from Minnesota, including one by our medicinal chemistry colleague, Chengguo Xing, who will be presenting a talk entitled “An Anticancer Drug Candidate against Drug-resistant Leukemia and Its Potential Mechanism of Action.” You can view the entire agenda here.

On Friday and Saturday, May 20 and 21, I’m delighted to be hosting my collaborator and friend, David Sherman (University of Michigan), in the Department of Chemistry for the Abbott Workshop in Synthetic Organic Medicinal Chemistry. David is world-renowned for his work in studying natural product biosynthesis, combinatorial biosynthesis, and metabolic engineering. David’s lecture, “Novel Drug Leads from Natural Products and their Derivation from Microbial and Biosynthetic Diversity”, will be held at 4:15 on Friday, May 20 in 331 Smith Hall. The more informal workshop session will be held from 10–12:30 on Saturday, May 21 in 117/119 Smith Hall.

LesFest Recap, Part 1

2011 Lester A. Mitscher Symposium

May 12–14, 2011

Lawrence, KS

University of Kansas, Pharmacy Building and Oread Hotel

Celebrating Professor Mitscher’s 80th birthday and his contributions to the field of medicinal chemistry and to the University of Kansas

Lester A. Mitscher

It’s hard to overstate the personal and scientific impact that Les Mitscher has had on medicinal chemistry and his students and postdocs during his nearly 45 years in academia. Affectionately dubbed “LesFest”, the Mitscher Symposium brought together former colleagues and group members from throughout Les’ long career to celebrate his 80th birthday and appointment as Emeritus Professor at the University of Kansas. The main events over the three-day program were a welcoming reception, a day-long symposium, and a banquet dinner.

The Organizing Committee for the event consisted of Dan Flynn (Ph.D. 1981, President and CEO, Deciphera Pharmaceuticals), Barbara Timmerman (Kansas), Brian Blagg (Kansas), and me (Ph.D. 1999, Minnesota), although Dan and his assistant, Anjanette Wilheim, did most of the work. Many others assisted with the planning, and everyone’s help is gratefully acknowledged. An amazing cast of plenary speakers spoke at the symposium: Stevan Djuric (Abbott Laboratories), Dale Boger (The Scripps Research Institute), Dan Flynn, George Ellestad (Columbia University), Ashok Bhatia (Abbott Laboratories), Gunda Georg (University of Minnesota), and me.

In Part 1 of my LesFest review, I’ll first summarize the impressive career and accomplishments of Les, then provide my thoughts about the welcoming reception on Thursday evening. In Part 2, I will review the oral presentations and banquet.

Les was one of Carl Djerassi’s first graduate students at Wayne State University, where he received his Ph.D. in Chemistry in 1958 for his work on the structure of coffee oil diterpenes and optical rotatory dispersion methods. From 1958–1967 Les worked at Lederle Laboratories as a natural product chemist, and rose to Group Leader of Antibiotic Discovery. He left Lederle for an appointment as Associate Professor of Natural Products Chemistry at The Ohio State University, where he was quickly promoted to Professor. In 1975, Les was recruited to Kansas as a University Distinguished Professor and Chair of Medicinal Chemistry. He remained Chair until 1992. Professor Mitscher has also held joint appointments at the University of Missouri-Kansas City and the Victorian College of Pharmacy (Melbourne, Australia). Over 50 students and postdocs were trained in the Mitscher lab, and Les has authored more than 280 research publications and 20 patents. He also authored or co-authored seven book on drug discovery, including several volumtes of the outstanding Organic Chemistry of Drug Synthesis series with Dan Lednicer. Les is the longest-serving consultant at Abbott Laboratories, and he consults extensively with several pharmaceutical companies and research organizations. He serves on the editorial board of numerous journals, and is a past Editor-in-Chief of Medicinal Research Reviews.

Always at the leading edge of drug discovery, the scope of Les’ work includes the discovery of clinically used antibiotics, key findings on the chemistry and mechanism of action of antibiotics and chemotherapeutic agents, herbal medicines, and the development of combinatorial chemistry methods. He is perhaps most well-known for his pioneering work on tetracyclines, quinolones, and erythromycin antibiotics.

As you might imagine, Les has been recognized with numerous honors and awards through his illustrious career, including: Smissman Award in Medicinal Chemistry (American Chemical Society), Volweiler Award (American Association for Pharmaceutical Education), Medicinal Chemistry Division Hall of Fame (American Chemical Society), Research Achievement Award in Natural Products Chemistry (American Pharmaceutical Association), Award in Medicinal Chemistry (American Chemical Society), Norman Farnsworth Research Achievement Award (American Society for Pharmacognosy), Fellow of the American Association for the Advancement of Science, and Emeritus Fellow of the International Union of Pure and Applied Chemistry.

This summary of Les’ accomplishments and impact on medicinal chemistry is not complete, and cannot do full justice to describing the lasting impact he has had. His current and former colleagues and group members can tell you many stories that provide insight as to what a wonderful, kind human being Les is.

You can probably gather the excitement I was feeling as my current graduate students (Mike Peterson, Will Fiers, and Yang Li) and I embarked on the seven-hour drive from Minneapolis to Lawrence. We had to wait for Will and Yang to finish their last final exam on Thursday morning, so we didn’t arrive to the Welcome Mixer at the Oread Hotel until about 8:00 pm after checking into our hotel and a quick change of clothes.

George Ellestad, Les Mitscher, and Dale Boger at the Welcome Mixer

Click on the picture to see more photos from the Mitscher Symposium.

The Oread is a beautiful, massive hotel located at the edge of the main campus, and the facilities there were top-notch. We ran into my dear friend Brian Blagg as we entered the lobby, and he helped point us to the back room where the reception was located. The room was filled with a celebratory air, and I quickly found Les and his lovely wife Betty to offer my congratulations. I was immediately struck by the outpouring of support for Les, as the room was filled with Kansas colleagues, symposium speakers, former group members, and KU alumni from other research groups. It was also great to catch up with alumni from my time at Kansas (1994–1999) such as Burchelle Blackman, Tim Caldwell, Suzanne Buck, and Jennifer Golden. Due to our late arrival, however, the reception ended too soon despite extending for nearly an extra hour. Since we didn’t have a chance to get dinner, my group and I left to catch at bite at Free State Brewery before calling it a night.

Les Mitscher and Dan Flynn at the Welcome Mixer

Click on the picture to see more photos from the Mitscher Symposium.

Coming in Part 2 of the LesFest recap: more pictures and a review of the symposium and banquet dinner, including my personal reflections on my time in his group.

Welcome to the Fecik Lab Blog Site

Welcome to the blog site for the Fecik laboratory at the University of Minnesota, Department of Medicinal Chemistry. I’ve struggled over the last couple of years with a webpage format that can be regularly updated and easy to maintain to provide information to the group about news and events both in the group and at Minnesota. After a couple of aborted attempts, I’ve finally settled on a traditional blog format. A seminar and event calendar will be added shortly, and updates and improvements will be rolled out as the site develops. Stop back for regular posts about group news and events of interest to medicinal chemistry at Minnesota.