Development of recombinant inhibitors specific to human kallikrein 2 using phage-display selected substrates
Details
Serval ID
serval:BIB_AA79106E3A7E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Development of recombinant inhibitors specific to human kallikrein 2 using phage-display selected substrates
Journal
European Journal of Biochemistry
ISSN
0014-2956
Publication state
Published
Issued date
02/2004
Peer-reviewed
Oui
Volume
271
Number
3
Pages
607-13
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Feb
Research Support, Non-U.S. Gov't --- Old month value: Feb
Abstract
The reactive site loop of serpins undoubtedly defines in part their ability to inhibit a particular enzyme. Exchanges in the reactive loop of serpins might reassign the targets and modify the serpin-protease interaction kinetics. Based on this concept, we have developed a procedure to change the specificity of known serpins. First, reactive loops are very good substrates for the target enzymes. Therefore, we have used the phage-display technology to select from a pentapeptide phage library the best substrates for the human prostate kallikrein hK2 [Cloutier, S.M., Chagas, J.R., Mach, J.P., Gygi, C.M., Leisinger, H.J. & Deperthes, D. (2002) Eur. J. Biochem. 269, 2747-2754]. Selected substrates were then transplanted into the reactive site loop of alpha1-antichymotrypsin to generate new variants of this serpin, able to inhibit the serine protease. Thus, we have developed some highly specific alpha1-antichymotrypsin variants toward human kallikrein 2 which also show high reactivity. These inhibitors might be useful to help elucidate the importance of hK2 in prostate cancer progression.
Keywords
Bacteriophages/*genetics
Base Sequence
Blotting, Western
DNA Primers
Humans
Hydrolysis
Kinetics
Mutagenesis, Site-Directed
Recombinant Proteins/pharmacology
Serine Proteinase Inhibitors/*pharmacology
Tissue Kallikreins/*antagonists & inhibitors
Pubmed
Web of science
Open Access
Yes
Create date
21/01/2008 17:10
Last modification date
20/08/2019 16:14