title: Developments in the design and synthesis of calpain inhibitors.
abstract: Calpains are Ca(2+)-dependent cysteine proteases that play an important role in cell differentiation and in apoptosis/necrosis. The overactivation of calpain is connected with a number of diseases, including cataracts and traumatic brain injury, making calpain an attractive drug target. The development of selective inhibitors of calpain has, however, proved difficult, due to a lack of detailed structural information on the protein. This difficulty has been somewhat alleviated with recent reports on the X-ray crystal structures of engineered calpains and improved biochemical characterization of the protein. This review describes properties and X-ray crystal structures of calpain, and the synthesis and binding affinities of novel calpain inhibitors.
authors.affiliation: University of Canterbury, Department of Chemistry, Christchurch 8020, New Zealand. axel.neffe@canterbury.ac.nz
authors.forename: Axel T
authors.initials: AT
authors.lastname: Neffe
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Abell
mesh_terms: D000447:Aldehydes / Q000138:chemical synthesis; D000577:Amides / Q000138:chemical synthesis; D001665:Binding Sites; D001713:Biphenyl Compounds / Q000138:chemical synthesis; D002154:Calpain / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D020128:Inhibitory Concentration 50; D010455:Peptides / Q000138:chemical synthesis; D011355:Prodrugs / Q000138:chemical synthesis*; D011487:Protein Conformation; D012995:Solubility
chemical_list: D000447:Aldehydes; D000577:Amides; D001713:Biphenyl Compounds; D015853:Cysteine Proteinase Inhibitors; D010455:Peptides; D011355:Prodrugs; D002154:Calpain