title: Molecular modeling, synthesis, and biological evaluation of macrocyclic calpain inhibitors.
abstract: The design and elaboration of a series of macrocyclic templates that exhibit a propensity to adopt a beta-strand-like peptide-backbone conformation led to potent and selective inhibitors of calpain 2. Macrocycle 1 retarded calcium-induced opacification in an ovine-lens culture assay and is a lead compound for the development of a drug for cataract treatment. Cbz=carbobenzyloxy.
authors.affiliation: Department of Chemistry, University of Canterbury, Private Bag 4800, Christchurch, New Zealand.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Abell
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Jones
authors.forename: James M
authors.initials: JM
authors.lastname: Coxon
authors.forename: James D
authors.initials: JD
authors.lastname: Morton
authors.forename: Steven G
authors.initials: SG
authors.lastname: Aitken
authors.forename: Stephen B
authors.initials: SB
authors.lastname: McNabb
authors.forename: Hannah Y-Y
authors.initials: HY
authors.lastname: Lee
authors.forename: Janna M
authors.initials: JM
authors.lastname: Mehrtens
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Alexander
authors.forename: Blair G
authors.initials: BG
authors.lastname: Stuart
authors.forename: Axel T
authors.initials: AT
authors.lastname: Neffe
authors.forename: Roy
authors.initials: R
authors.lastname: Bickerstaffe
mesh_terms: D000818:Animals; D002154:Calpain / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002386:Cataract / Q000139:chemically induced / Q000188:drug therapy; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry; D020128:Inhibitory Concentration 50; D007908:Lens, Crystalline / Q000378:metabolism; D047028:Macrocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D012756:Sheep; D013329:Structure-Activity Relationship
chemical_list: D015853:Cysteine Proteinase Inhibitors; D006571:Heterocyclic Compounds; D047028:Macrocyclic Compounds; C106058:macrocycle 1; D002154:Calpain