Peptide-Based Drug Design

6 Otvos
was designed based on ligand-binding models of the Grb2 SH2 protein domain
(30). As a third example, paper-bound peptide arrays identified nanomolar
antagonists to E-selectin in vitro with ensuing inhibition of lung metastasis at
a 30 mg/kg single dose in vivo (31). Chapter 6 presents the state of the art in
the nuclear magnetic resonance (NMR) structural analysis of peptides and their
interactions with target molecules. If the conformations involved are known, we
can switch to computer-assisted de novo design of potent agonists or antagonists,
as described in Chapter 7. Finally, if the computer modeling does not provide
peptides with the expected activities in the molecular assays, high-throughput
screening on peptide macroarrays, as outlined in Chapter 4, can come to rescue.
Actually, I truly believe that the concomitant use of all these designing and
screening techniques together with the rest of the methodologies presented in
this book will offer the greatest hope for the successful development of many
peptide-based drugs to save or improve our lives and those of our companion
animals.
References
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