Cysteine proteinase inhibitors as therapy for parasitic diseases: advances in inhibitor design.
Clan CA (papain-like) cysteine proteinases of protozoan parasites are validated targets for the rational design of new anti-parasitic chemotherapies. Peptidyl and peptidomimetic proteinase inhibitors of differing chemistries limit parasite survival in vitro and in vivo. Also, the development of activity-based affinity labels has enabled the identification and characterization of potential cysteine proteinase targets in situ. This article reviews the biology and physicochemistry of parasite proteinases and the ongoing design of peptidyl and non-peptidyl inhibitors to generate anti-parasitic compounds of greater efficacy with decreased toxicity to the host.
Steverding
Dietmar
D
Biomedical Research Centre, School of Medicine, Health Policy and Practice, University of East Anglia, Norwich NR4 7TJ, UK. dsteverding@hotmail.com
Caffrey
Conor R
CR
Sajid
Mohammed
M
D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D010272:Parasitic Diseases / Q000188:drug therapy*; D013329:Structure-Activity Relationship
D015853:Cysteine Proteinase Inhibitors