Novel reagents and reactions for drug design*
T. J. Baker, Y. Rew, and M. Goodman**
Department of Chemistry and Biochemistry, University
of California, San Diego, La Jolla, California 92093-0343, USA
Abstract: In this presentation, we cover new results from two
of our synthetic endeavors: guanidinylation reagents and novel bridged
opioids. In the first part, we describe the applications of the diurethane-triflylguanidines
to prepare target bioactive structures including peptides, heterocyclic
drugs, and aminoglycoside derivatives. The formation of novel guanidinoglycosides
led to a family of effective binders to the RNA recognition element
of the HIV-1 Rev protein. In the second part, the syntheses of sulfur
and amine-bridged cyclic opioids is described. These analogs exhibit
enhanced binding, both in vitro and in vivo. Specifically,
H-Tyr-c[D-ValL
-Gly-Phe-D/L-AlaL
]-OH (ValL and AlaL
denote the lanthionine amino acid ends linked by a monosulfide bridge)
is potent and highly d -receptor selective
while Tyr-c[(Ng CH3 )-D-A2
bu-Gly-Phe-NHCH2CH2 -] though nonselective is
one of the most potent opioids prepared to date. These molecules are
representative of our design of novel peptidomimetic opioids.
*Lecture presented at the 5th International
IUPAC Symposium on Bioorganic Chemistry (ISBOC-5), Pune, India, 30 January
- 4 February, 2000.
**Corresponding author
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