Phage display screening for peptidic chitinase inhibitors.
A phage display library with disulfide-cyclized peptides was screened for peptides binding to chitinases from Serratia marcescens. One of those peptides was found to efficiently inhibit chitinase A and two others were inhibitors of chitinase B. Complete substitutional analysis of all three peptides using cellulose-bound peptide spot synthesis revealed key interaction positions and allowed optimization of the chitinase B inhibitory peptides towards higher affinity, with inhibitory constants in the lower nanomolar range. Inhibition by all peptides proved to be competitive and highly specific for the chitinase used to select them, as shown with a series of chitinases from different organisms.
Petter
Cordula
C
Institute of Biochemistry, Charité- Universitätsmedizin Berlin, Monbijoustrasse 2, D-10117 Berlin, Germany.
Scholz
Christa
C
Wessner
Helga
H
Hansen
Gerd
G
Henklein
Peter
P
Watanabe
Takeshi
T
Höhne
Wolfgang
W
D002688:Chitinases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D019151:Peptide Library
D004791:Enzyme Inhibitors; D019151:Peptide Library; D002688:Chitinases