title: Synthesis and enzyme inhibitory activities of novel peptide isosteres.
abstract: Design and synthesis of metabolically stable peptide analogs that can either mimic or block the bioactivity of natural peptides or enzymes is an important constituent of bioorganic and medicinal chemistry research. Isosteric replacement of a scissile peptide bond represents a viable and popular approach in the rational design of peptidomimetics. Peptidomimetics find applications as drugs, in protein engineering and so on. This is evident from the wealth of therapeutically useful peptidomimetic leads incorporating any of the peptide isosteres that are currently available. In this review, we have given a brief account of the types of peptide isosteres widely known till date. With this background, we have described some of the recent developments in synthetic approaches. This includes methods involving a common intermediate to synthesize different possible isosteres and their peptide analogs, solid phase synthesis and combinatorial approach. One such method involving stereoselective nitrile oxide cycloaddition as the key step has been studied extensively in our research laboratory. Finally, we have also discussed about some of the recent reports on the design and inhibitory activities of peptidic or non-peptidic analogs against aspartic proteases (HIV-1, renin, ACE and pepsin) and peptide analogs of an immunomodulating hexapeptide.
authors.affiliation: National Research Lab, Department of Chemistry, Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Korea.
authors.forename: Natarajan
authors.initials: N
authors.lastname: Venkatesan
authors.forename: Byeang Hyean
authors.initials: BH
authors.lastname: Kim
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors; D020650:Combinatorial Chemistry Techniques; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016333:HIV Protease / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010434:Pepsin A / Q000037:antagonists & inhibitors; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004791:Enzyme Inhibitors; D017320:HIV Protease Inhibitors; D010455:Peptides; D016282:Aspartic Acid Endopeptidases; D016333:HIV Protease; D010434:Pepsin A