title: Molecular modeling: a search for a calpain inhibitor as a new treatment for cataractogenesis.
abstract: Studies of 17 analoges of 3 (SJA6017) in an in silico calpain model are reconciled to measured IC(50) values against ovine calpain. The studies validate the potential of the "model" and criteria established for inhibition as a tool to select structures for synthesis to test as calpain inhibitors. Using this screening methodology of virtual libraries led us to synthesize several inhibitors including macrocycle 33, which in vitro sheep eye lens culture experiments showed to substantially slow opacification.
authors.affiliation: Univesity of Canterbury, Christchurch, New Zealand.
authors.forename: Blair G
authors.initials: BG
authors.lastname: Stuart
authors.forename: James M
authors.initials: JM
authors.lastname: Coxon
authors.forename: James D
authors.initials: JD
authors.lastname: Morton
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Abell
authors.forename: D Quentin
authors.initials: DQ
authors.lastname: McDonald
authors.forename: Steven G
authors.initials: SG
authors.lastname: Aitken
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Jones
authors.forename: Roy
authors.initials: R
authors.lastname: Bickerstaffe
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002154:Calpain / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D020134:Catalytic Domain; D002386:Cataract / Q000517:prevention & control*; D016208:Databases, Factual; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007908:Lens, Crystalline / Q000187:drug effects / Q000473:pathology; D047028:Macrocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D012756:Sheep; D013329:Structure-Activity Relationship; D046509:Tissue Culture Techniques
chemical_list: D004151:Dipeptides; D047028:Macrocyclic Compounds; C109145:N-(4-fluorophenylsulfonyl)-L-valyl-L-leucinal; D002154:Calpain