netLibrary - eBook Summary Structure-based Drug Design by ...

Document
Figure 7
Convergent pathways in peptide, peptidomimetic, and nonpeptide drug
discovery
Page 570
using receptor-targeted peptide ligands or “second generation” agonist or antagonist analogs to develop
pharmacophore models (see Figure 3). However, this represents only a part of the sophisticated
convergent pathways that exist currently to advance both peptidomimetic and nonpeptide drug discovery
(Figure 7). In this scenario both native and foreign (biological or chemical origin) peptides may provide
the opportunity for ligand structure-based drug design. From pharmacophore models of key peptide
leads the iterative transformation to peptidomimetic “second generation” analogs may proceed through
either peptide scaffold-or nonpeptide template-based approaches. Examples of such work are detailed
below.
Independent of the hierarchial approach to peptide ligand structure-based design of peptidomimetics is
the work that encompasses screening-based nonpeptide lead discovery. Such nonpeptides may be of
chemical or biological origin (see below), and historically have been identified by targeted or random
screening approaches. Although they are not designed to be peptidomimetics in the chemical structure
sense, many appear to be biological mimics (e.g., receptor agonists or antagonists, protease inhibitors,
signal-transduction protein inhibitors, or antagonists) of a known native or foreign peptide. And, in few
http://legacy.netlibrary.com/nlreader/nlReader.dll?bookid=12640&filename=Page_570.html [4/9/2004 1:08:04 AM]