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
Author(s)
Cloutier  S. M., Kundig  C., Felber  L. M., Fattah  O. M., Chagas  J. R., Gygi  C. M., Jichlinski  P., Leisinger  H. J., Deperthes  D.
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
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 16:10
Last modification date
20/08/2019 15:14
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