Meeting/Event Information

    “Drugging the Un-Druggable: Discovering Small Molecule Inhibitors of Constitutive Protein-Protein Interactions”, Adrian Whitty - Boston U.

    June 23, 2011
    5:00 PM - 9:30 PM
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    The Country Squire
    19133 E. Belvidere Rd.
    Grayslake, IL 60030
     Directions

    Abstract:  Inhibiting protein-protein interactions (PPI) with small molecules represents a major challenge for contemporary drug discovery and chemical biology.  Disrupting constitutive, high-affinity protein oligomers in some ways represent an extreme form of this challenge.  We describe two synthetic inhibitors of different trimeric TNF-family cytokines - TNFalpha and CD40 Ligand - that were discovered independently using conventional binding or inhibition assays, but were subsequently found to function by disrupting the trimeric structure of these high affinity, constitutive oligomers.  The X-ray co-crystal structure of each compound with its target revealed important similarities and striking differences in the mode of recognition.  Detailed biochemical and biophysical characterization suggests that the inhibited complexes represent different stages of a common inhibition mechanism involving a conserved core of aromatic residues. Overall, our results suggest that constitutive PPI interfaces can in some cases be easier to inhibit with a small molecule than are weaker, transient PPI targets.

    Biography: Dr. Whitty is Associate Professor in the Department of Chemistry, Boston University, where he joined the faculty in 2008.  He spent the previous 14 years at Biogen Idec, most recently as Director of Physical Biochemistry leading a group responsible for the structural, biophysical and mechanistic study of drug targets and of protein and small molecule drug candidates.  He obtained a B.Sc. in Chemistry at King’s College, University of London and a Ph.D. in Organic Chemistry at the University of Illinois at Chicago, after which he held a Postdoctoral Fellowship at Brandeis University with Professor William P. Jencks.  He left Brandeis to join Biogen (now Biogen Idec) in 1993.  His research has included elucidation of enzyme mechanisms and enzyme-inhibitor interactions, as well as mechanistic investigations of integrins, immune cell co-stimulatory molecules, and a number of cytokine and growth factor receptors.  The unifying theme of his work has been to understand how binding energy is generated through protein-protein or protein-small molecule interactions, and how it is used to achieve biological function and specificity.  A major current focus of his research is the development of small molecule inhibitors that block protein-protein interactions.

    Pre-Dinner Talk by Rudy Bernath:

    “The History of the Chicago Chemists Club.  How does it relate to today's chemists, the ACS, and where are we headed?”

     

    Distinguished Service Award

    David Crumrine

    Prof. David CrumrineThe Distinguished Service Award recognizes members for outstanding and dedicated service to the Chicago Section ACS. The winner of this year’s award is David Crumrine.

    David’s interest in Chemistry was primed partly by his parents who taught Science, Math and some other classes in several Ohio high schools.  After one summer in an NSF high school chemistry program at Northern Illinois University, a summer NSF research opportunity at Ohio State with Albert Padwa, and a summer spent in Nitro, WV working for Monsanto with John Damico, his course was set. A PhD in organic photochemistry with H. E. Zimmerman from U of Wisconsin-Madison was followed by Post-doctoral work with Herb House at MIT and Georgia Tech.

    David’s initial ACS membership was part of a Senior award from Ashland College. Participation in the Chicago ACS Section was encouraged by two Loyola colleagues Carl Moore and Bruno Jaselskis. He worked on the Special topics committee arranging predinner talks, the high school Education Committee, and, since 1997, the Chemistry Day Committee, sometimes as co-chair with Tom Kucera.  With the help of Loyola colleagues, he has administered both the Local and National Chemistry Olympiad exams at Loyola since 2002.

    David served as Chair of the Chicago Section in 2008. He served on the 21st ACS GLRM committee, which met at Loyola University Chicago in 1987, as Program co-chair of the 30th GLRM in 1997, as Program Chair for the 35th GLRM, and Program co-chair for the 38th GLRM held in Lincolnshire in 2009.  He has been an ACS Chicago councilor since 2001.  In that position, he has served on the ACS Publications committee (2002 – 2004) and subsequently on the Committee on Chemical Safety, and he has chaired the Resources Subcommittee for several years. 

    In 1994 David organized, with David Boykin, an international symposium on Group VI NMR at the Washington ACS meeting, and in 2007 organized, with Laren Tolbert and Steve Fleming, an international symposium honoring H. E. Zimmerman’s work at the Boston ACS meeting.

    David started at Loyola University working on N-nitrosamine photochemistry and reaction mechanisms, and taught 6 different classes in 1.5 years before he repeated one. A year’s leave to learn more about NMR Spectroscopy working first with Hiizu Iwamura of the Institute of Molecular Science in Ozkazaki, Japan and then with Gordon Lowe of The Dyson-Perrins Laboratory at Oxford University in 1980-81 was a big plus for the whole family, and a break into Oxygen and Sulfur NMR.  The fall semester 2007 spent with Manuel Diaz of the Cancer Center at Loyola University Medical Center helped him to learn more about research and techniques related to cancer biology.  He has published 37 refereed research papers and two review articles working with outstanding graduate students, undergraduate students, and colleagues.

    David was named a Master Teacher of the college of Arts and Sciences at Loyola University in 2004 and was nominated again in 2009.  He was asked to join the Office of Research Services in 1997 where he was in charge of handling grant applications and awards and responsible for committees such as IRB, IACUC, and Radiation Safety.  He became Asst. VP for Research before returning full time to Chemistry to be Chair from 2002 to 2006.  This position afforded him the opportunity to interact with the Chemistry Chairs of other Jesuit Universities from around the world.

    In fall 2010 David was asked to be the Acting Director of CUERP (The Center for Urban Environmental Research and Policy), which produces biodiesel fuel and is involved with Sustainability issues.  He currently serves on a number of University Committees.

    A large number of colleagues and friends, research leaves to Japan, England, and Europe, trips with Jesuit chairs to Belgium and Spain, Regional and National ACS meetings, various Chemistry conferences, and a recent graduate reunion in Ireland were all very pleasing consequences of David’s career. 

    David and his wife Sheila enjoy their combined families and share Dave’s 94 year old mother, their 4 sons, two daughters-in-law, a granddaughter due in May and a wonderful life together.

    Cost:  $30.00 for members of ACS and their guests, $32.00 for non-members, and $15 for students, retired, or unemployed

    Dinner reservations are required and should be received in the Section Office via phone (847-391-9091), email ([email protected]), or web by noon on Tuesday, June 21.   PLEASE HONOR YOUR RESERVATIONS.  The Section must pay for all food orders.  No-shows will be billed.  Seating will be available for those who wish to attend only the meeting.

      Please  REGISTER ON LINE 

    5:00 - 6:00 PM · Job Club
    5:30 - 6:15 · Pre-Dinner Talk
    5:30 - 6:30 PM · Social Hour
    6:30 - 7:30 PM · Dinner
    7:30 PM · General Meeting


    Map and Directions

    Parking:   Large parking lot on the premises


    Dinner:

    • Fresh Fruit Cocktail
    • Spinach Salad
    • Entrées (choose one):
      • Roast Prime Rib
      • Broiled Lake Superior White Fish
      • Pasta with Vegetables
    • Baked potato
    • Stuffed Tomato w/Broccoli au Gratin
    • Cheesecake w/Strawberry Topping for dessert

     

    Tickets

    $37.00 Member

    $39.00 Non-member

    $20.00 Student/Unemployed/Retired

    $0.00 Cash at the door: $35 member/ $37 nonmember/ $20 student/retired/unemployed