title: New β-strand templates constrained by Huisgen cycloaddition.
abstract: New peptidic templates constrained into a β-strand geometry by linking acetylene and azide containing P(1) and P(3) residues of a tripeptide by Huisgen cycloaddition are presented. The conformations of the macrocycles are defined by NMR studies and those that best define a β-strand are shown to be potent inhibitors of the protease calpain. The β-strand templates presented and defined here are prepared under optimized conditions that should be suitable for targeting a range of proteases and other applications requiring such a geometry.
authors.affiliation: School of Chemistry & Physics, The University of Adelaide, North Terrace, Adelaide SA 5005, Australia.
authors.forename: Ashok D
authors.initials: AD
authors.lastname: Pehere
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Abell
mesh_terms: D000447:Aldehydes / Q000138:chemical synthesis / Q000494:pharmacology; D002154:Calpain / Q000037:antagonists & inhibitors; D003500:Cyclization; D047028:Macrocyclic Compounds / Q000138:chemical synthesis; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
chemical_list: D000447:Aldehydes; D047028:Macrocyclic Compounds; D010455:Peptides; D011480:Protease Inhibitors; D002154:Calpain