DESIGN OF SENSITIVE FLUOROGENIC SUBSTRATES FOR HUMAN CATHEPSIN-D

Citation
Sv. Gulnik et al., DESIGN OF SENSITIVE FLUOROGENIC SUBSTRATES FOR HUMAN CATHEPSIN-D, FEBS letters, 413(2), 1997, pp. 379-384
Citations number
25
Categorie Soggetti
Biophysics,Biology
Journal title
ISSN journal
00145793
Volume
413
Issue
2
Year of publication
1997
Pages
379 - 384
Database
ISI
SICI code
0014-5793(1997)413:2<379:DOSFSF>2.0.ZU;2-R
Abstract
Cathepsin D is a lysosomal aspartic proteinase that has been implicate d in several pathological processes such as breast cancer and Alzheime r's disease, We designed and synthesized a number of quenched fluoroge nic substrates with P2 variations in the series AcEE(EDANS)KPIXFFRLGK( DABCYL)E-NH2, where X=cysteine, methylcysteine, ethylcysteine, tert-bu tylcysteine, carboxymethylcysteine, methionine, valine or isoleucine, Most of the fluorogenic substrates exhibited greater k(cat)/K-m ratios than the best cathepsin D substrates described so far, Differences in kinetic constants, which were rationalized using structure-based mode ling, might make certain substrates useful for particular applications , such as active site titrations or initial velocity determination usi ng a fluorescent plate reader, (C) 1997 Federation of European Biochem ical Societies.