Conformationally constrained inhibitors of caspase-1 (interleukin-1 beta converting enzyme) and of the human CED-3 homologue caspase-3 (CPP32, apopain)

D S Karanewsky; X Bai; S D Linton; J F Krebs; J Wu; B Pham; K J Tomaselli

doi:10.1016/s0960-894x(98)00498-3

Conformationally constrained inhibitors of caspase-1 (interleukin-1 beta converting enzyme) and of the human CED-3 homologue caspase-3 (CPP32, apopain)

Bioorg Med Chem Lett. 1998 Oct 6;8(19):2757-62. doi: 10.1016/s0960-894x(98)00498-3.

Authors

D S Karanewsky¹, X Bai, S D Linton, J F Krebs, J Wu, B Pham, K J Tomaselli

Affiliation

¹ Idun Pharmaceuticals, La Jolla, CA 92037, USA.

PMID: 9873617
DOI: 10.1016/s0960-894x(98)00498-3

Abstract

A systematic study of interleukin-1 beta converting enzyme (ICE, caspase-1) and caspase-3 (CPP32, apopain) inhibitors incorporating a P2-P3 conformationally constrained dipeptide mimetic is reported. Depending on the nature of the P4 substituent, highly selective inhibitors of both Csp-1 or Csp-3 were obtained.

MeSH terms

Caspase 3
Caspase Inhibitors*
Cysteine Proteinase Inhibitors / chemical synthesis*
Cysteine Proteinase Inhibitors / chemistry
Cysteine Proteinase Inhibitors / pharmacology*
Dipeptides / chemical synthesis
Dipeptides / chemistry
Dipeptides / pharmacology
Humans
Molecular Conformation
Oligopeptides / chemical synthesis*
Oligopeptides / chemistry
Oligopeptides / pharmacology*
Structure-Activity Relationship

Substances

Caspase Inhibitors
Cysteine Proteinase Inhibitors
Dipeptides
Oligopeptides
CASP3 protein, human
Caspase 3