N-heterocyclic dipeptide aldehyde calpain inhibitors.
A series of Val-Leu based peptidic aldehydes containing either a furan or thiophene at the N-terminus was prepared and assayed against ovine m-calpain. In general, potency is favoured by a 2-substituted (rather than 3-substituted) heterocycle, a thiophene rather than a furan, and a shorter chain length at the N-terminus. Molecular docking experiments provide some rationale for these observations.
Jones
Seth A
SA
School of Chemistry & Physics, University of Adelaide, North Terrace, Adelaide, SA 5005, Australia.
Jones
Matthew A
MA
McNabb
Stephen B
SB
Aitken
Steven G
SG
Coxon
James M
JM
Abell
Andrew D
AD
D000447:Aldehydes / Q000737:chemistry; D000818:Animals; D002154:Calpain / Q000037:antagonists & inhibitors*; D004151:Dipeptides / Q000737:chemistry / Q000494:pharmacology*; D005663:Furans / Q000737:chemistry; D006023:Glycoproteins / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D012756:Sheep; D013876:Thiophenes / Q000737:chemistry
D000447:Aldehydes; D004151:Dipeptides; D005663:Furans; D006023:Glycoproteins; D010456:Peptides, Cyclic; D013876:Thiophenes; C039304:calpain inhibitors; C041390:valylleucine; D002154:Calpain; C449000:m-calpain; C039281:furan