Subject: Seeking examples ....

From: "Hr Dr. S. Shapiro" <[email-masked]>
Date: Thu, 11 Apr 1996 07:58:42 +0100 (MET)

Dear Colleagues;

     Suddenly and on very short notice I have been requested to make a "sales
pitch" relating to the usefulness of receptor structures (as determined by
X-ray crystallography or perhaps other means) _OR_ receptor models/theoreti-
cal receptor structures (such as mini- or pseudoreceptor surrogates derived
from QSAR data) vis-a'-vis drug design.

     I therefore request that anyone who can provide specific and concrete
examples (including references to relevant publications and/or patents) of
drugs and/or useful "biologicals" whose development was substantially facili-
tated by knowledge of actual or postulated receptor structures to please for-
ward that information to me as soon as possible.

     I shold point out that I am particularly interested here in antimicro-
bial agents, but I would be grateful to receive information on _any_ sorts of
drugs or "biologicals" whose development was substantially facilitated by
knowledge of actual or postulated receptor structures.

     The structure of the target site for beta-lactam antibiotics such as the
penicillins, cephalosporins, and cephamycins is well known.  Are there any
examples of new beta-lactams which have been designed on the basis of detail-
ed knowledge of the target site?  Likewise, are there any examples of clavu-
lanic acids or other beta-lactamase inhibitors which were designed either in
whole or in part on the basis of information regarding their binding to beta-
lactamases?  Again, references are important.

     Thanks in advance to all responders, from whom I hope to soon hear.

Sincerely,

S. Shapiro
ZH
[email-masked]