Transistion State Analogs

Louis Hom lhom at OCF.Berkeley.EDU
Wed Feb 1 11:58:48 EST 1995


I'm looking for some good reviews on transition state analog design (for use
in developing catalytic antibodies).  I've read Neil Thomas' paper (App Biochem
& Biotech 47:345-75), but I'd like to have some additional sources.  Any
recommendations?
	For the curious, I'd like to design a transition state analog for the
xanthine phosphoribosyltransferase (XPRT) reaction:

                               O                            
                              ||                            
                             /  \                           
                        N - C    NH                         
                       ||   ||   |                          
                       HC   C    C=O			
                        \  / \  /                       
                         N     N                           
                        H:     H                           
          O              :                                 
         ||     H    O   :  H                               
      -O--P--O--CH/    \ : /                               
          |     |/      \v/                                
          O-    C        C                                 
                |\ H  H /|  O     O                          
                H \|  |/ |  ||    ||                               
                   C--C  O--P--O--P--O-                                 
                   |  |     |     |                          
                  HO  OH    O-    O-              

I'm wondering if replacing the 1'C of the ribose would lead to an unstable
compound.  On the one hand, NTP hydrolysis is a spontaneous reaction, but then
putting a P at 1' wouldn't really yield a triphosphate.  Maybe I should look
for a different 5-center atom? 
-- 
______________________________________________________________________________
Lou Hom		     		"Few things are harder to put up with than 
lhom at ocf.berkeley.edu		 the annoyance of a good example." - Mark Twain
http://www.ocf.berkeley.edu/~lhom/ 



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