Chapter 26. Approaches to the Discovery of Non-Peptide Ligands for Peptide Receptors and Peptidases

摘要: Publisher Summary This chapter discusses the recent advances in various strategies available for discovery of non-peptide ligands, such as peptide mimetics, receptors and peptidases. Empirical approaches to ligands have involved screening pure compounds complex mixtures biological assays. The entities has generally afforded little reported success, with exception promiscuous μ-opioid receptor. receptor proved be more elusive. Apart from report a structurally uncharacterized bradykinin antagonist Mandevilla relutina , CCK asperlicin remains single significant success. Several new applications conformationally restricted amino acids been described this chapter. Analogues containing amide bond surrogates frequently utilized investigate aspects structure function. Recently, several improved syntheses (E)-alkene mimetics appeared, which good stereochemical control appropriate peptidic side chains was achieved. design, synthesis, pharmacology novel dipeptide recently described. In all preceding, mimics seek duplicate configuration trans-amide bond. An intriguing challenge mimetic design is structures that can model 3-dimensional orientation acid residues into known secondary conformations proteins: turns, helices, sheets. β-sheet α-helix also discussed goal mimicry structural leads or development molecular result bioavailable analogues. Although it may not necessary remove peptide-like character ach eve objective, reduction weight resistance peptidase action required.