xt7nzs2k9f04 https://exploreuk.uky.edu/dips/xt7nzs2k9f04/data/mets.xml University of Kentucky University of Kentucky Chemistry Department 19900416 A brochure for the Naff Symposium, an event hosted by the University of Kentucky Chemistry Department supported by the Anna S. Naff Endowment Fund. This brochure belongs to the University of Kentucky Chemistry Department Records collection, accession number 2014ua075. archival material  English University of Kentucky Chemistry Department Contact the Special Collections Research Center for information regarding rights and use of this collection. University of Kentucky Chemistry Department Naff Symposium brochures Sixteenth Annual Symposium on Chemistry and Molecular Biology: "Molecular Recognition" text Sixteenth Annual Symposium on Chemistry and Molecular Biology: "Molecular Recognition" 1990 2017 true xt7nzs2k9f04 section xt7nzs2k9f04 W
1990 PROGRAM E: E Q Sixteenth Annual
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____—____._______ .3 g g Symposmm on
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AM. PM. P ‘C 5
9:00 Registration and Coffee—Room 137, 12:15 Buffet Lunch, Faculty Club (Please return x 9... H‘ .
Chemistry-Physics Building card by April 7, 1990 for reservations. Cost ‘c x 90-. emls ry
$6.00t b aidatr itrti . 0
9:30 Welcome by Dr. Robert Hemenway, o e p es s a on ) 3 a 9
Chancellor, University of Kentucky, Room 1:30 Dr. Steven C. Zimmerman, University of 01 g (D
139, Chemistry-Physics Building Illinois 8 x- a.
940 l i: d t R k Chemically Synthesized Mimics of Biological . ‘C (,9f
' n o uc ory emar s Receptors and Enzyme Catalysts. 8 \2
9:45 Dr. Andrew D. Hamilton, University of . . . 01
Pittsburgh Noncovalent interactions are of fundamental importance to all 0" o e C“ ar
New Artificial Receptors for C o mplex ati o n biological processes. The efficiency of enzymatic catalysis and the
and Catalysis binding specificity of antibodies depends upon a large number of
_ . . g _ complementary intermolecular contacts. A promising approach .
An Important goal in modern bioorganic chemistry concerns . . . .
_ . _ . to understanding the nature of these noncovalent interactions is l
the desrgn of synthetic molecules that mimic various aspects of . .
h , D .1 d d f h d l l d through the study of chemical model systems. in this laboratory
enzyme. c .ehmistry. hetai e stu fy o suc mo ebs ca? ea ”Ct we have studied models for both biological “receptors” and for
0;: y t? "1mg ts mt? f1 6 "at“: : enzyme-acne: ut a so to ”elf" enzymic catalysis. The synthetic receptors have been designed to '9 .
c emica speCies “.“t some 0 t e speCi lefty an speed norma y complex aromatic substrates using only aromatic 1r-stacking in- | a Q
assoc1ated only With enzymes. Our approach has been to focus . . . . . . N r" N |N H MANN
. ‘ . , _ teractions, or a combination of 7r-stacking interactions and H--'"‘{;~” firs”
on biologically Significant substrates and to construct complemen- h . . . ’ __...N. —. 0:" .-N=’
. . , , . . . . ydrogen bonding. These studies have shown that a very high 0 H m— 0-H
tary receptors containing multiple binding interactions. In particular, . . . . . . __
. . g . degree of cooperatIVity can be obtained between multiple binding n N ..
we have incorporated several hydrogen bonding Sites into a . . . . . ‘ *
. , . . interactions. We have also developed a new model of the histidine- | Q .|
macrocyclic framework to provrde a highly selective receptor for . . . ”'2" ’ my; ,
. aspartate couple which contains a syn oriented carboxylate. Several
barbiturates. The approach has been extended to other substrates . .
_ , . . . enzymes, which have evolved independently, have been found
including urea, small peptides and the different nucleotide bases. to contain aspartic acid residues hydrogen bonded to catalytical- . .
Artificial receptors of this type may lead to the development of l t' h' t’d’ 'd P . ll 1 l . . fth established in the memory Of
1 harmaceutical strategies drug delivery systems or chemical y ac we 15 1 me resi ues. reVious sma mo ecu e mimics 0 e A S N ff
nove p . ’ His-Asp couple have constrained the carboxylate to an anti orienv nna - a
sensor deSigns. . . . . . . .
tation, while only the syn orientation is found in the enzymatic
10:45 Discussion system. __—_._.._—___—
10:50 Dr. William F. DeGrado, Central Research 2:40 Discussion M OLE CUL R
;::E:::I::;né:t Dept., E'l' du Pont de 2:50 Dr. Ronald Breslow, Columbia University I x
' Geometric Control of Binding and Catalysis
De Novo Desi n of Helical Proteins.
g . Multipoint binding interactions lead to increased affinity and RECOGNITION
Our group has recently adopted a synthetic approach to . . . .
, . , , multifunctional catalysis leads to increased rates. Both can pro» ________——
understanding the structural baSlS for protein function. In order . . . .
_ . duce increased selectiVities for substrates and products. Examples
to test some of the rules and concepts which are believed to be . . . . . . . .
, , . . . . from the first area include ditopic binders With antibody-like af-
important for protein folding and stability we are attempting to . . . . . . . . SPEAKERS
. , . _ _ , finities, and ditopic functionalizmg catalysts. Examples from the
design some Simple proteins which should fold into predetermined l . l d l . h' h b‘f . l l . .
three-dimensional structures Two types of helical roteins have atter area incu e examp es m w m iunctiona cata ySis ‘5
. . _ f _ , p . geometrically controlled in transaminase and nbonuclease mimics. Ronald Breslow
been designed: the first is an idealized verSion of a four-helix bun— . . . . . , .
. , _ Rigid binding can be useful for rate accelerations, but some Wllllam F DeGrado
dle, a folding pattern found in the structures of a variety of natural fr . '
, , . . eedom of motion must be left so the molecular complex can adapt .
water-soluble proteins including myohemerythnn, cytochrome C, h h . . d d f h . h W ‘1] Andrew D. Hamllton
d a oferittin while the other class of designed proteins is meant to t e c anging geometric eman s o t 2 reaction pat ' e W -
an .13, ’ . ‘ , describe an example of the rate improvement that this principle Steven C. Zimmerman
to mimic the structures of proteins which form ion channels such
‘ , , . leads to.
as the acetylcholine receptor. The syntheSis and characterization
of these proteins are currently underway and will be the focus of 3:50 Discussion
the talk. .
4:00 Mixeh Monday, April 16, 1990
: Di i .
11 50 “"55 °" Department of Chemistry
University of Kentucky
Lexington, Kentucky 40506—0055

 Sixteenth Annual Symposium on
C h e mis try &
established in the memory of Anna S. Naff
Monday, April 16, 1990, 9:00 a.m.
Chemistry-Physics Building—Room 139
Department of Chemistry, University of Kentucky
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Ronald Breslow, Ph.D., Harvard Univer- William C- DeGrado, PhD. The Univer-
sity. S.L. Mitchill Professor of Chemistry, Col- sity of Chicago. Research Leader, E.I. du Pont
umbia University. Member of the National de Nemours & CO- Adjunct Professor 0f
Academy of Sciences, the American Academy Biophysics, Johns Hopkins Medical School.
of Arts and Sciences, and the American Associate Editor, Proteins, Structure, Function,
Philosophical Society. Recipient of; Centenary Genetics. Editorial Board: Journal American
Medal from the British Chemical Society (1972); Chemical Society; Journal of Molecular
James Flack Norris Prize in Physical Organic Recognition; International Journal of Peptide
Chemistry from the American Chemical Socie- and Protein Research; Protein Engineering.
ty (1980); Arthur C, Cope Award from the Recipient: Du Vigneaud Award for Young In-
American Chemical Society (1987) and vestigators in Peptide Research; Protein Socie—
numerous other awards. Topic: “Geometric ty Young Investigator Award. Topic: “De Novo
Control of Binding and Catalysis.” Design of Helical Proteins.”

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Steven C. Zimmerman, Ph.D. Columbia Andrew D. Hamilton, Ph.D. Cambridge
University. NATO postdoctoral fellowship, Cam- University. NATO postdoctoral fellowship,
bridge University. Professor, University of II- Strasborg, France. Professor, University of Pitt-
linois. Presidential Young Investigator Award, sburgh. Visiting Professor of Chemistry, Univer-
National Science Foundation; Camille and sity of Kyoto (1987). Recipient of awards from
Henry Dreyfus Teacher-Scholar Award and Eli the Exxon Educational Foundation and Mobil.
Lilly Grantee. Topic: “Chemically Synthesized Topic: “Molecular Recognition: New Artificial
Mimics of Biological Receptors and Enzyme Receptors for Complexation and Catalysis”.
Catalysts.”

Parking available free at Commonwealth Stadium on Cooper Drive. Shuttle buses run to the main campus. Additional parking 1
(for a fee) available in UK Medical Plaza Parking Garage, located approximately one block south of the Chemistry-Physics
Building; this garage can be accessed from both Rose and Limestone Streets—look for Medical Plaza Parking signs. For addi-
tional information, call John Richard, Department of Chemistry, (606) 257-1285.
Symposium supported by the Anna S. Naff Endowment Fund.