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1990 PROGRAM E: E Q Sixteenth Annual
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________._______ .3 g g Symposmm on
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3 7:; 3
AM. PM. P C 5
9:00 Registration and CoffeeRoom 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--'"{;~ rs
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' td '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::;n: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 bf . 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 405060055