A peptide hydroxamate library for enrichment of metalloproteinases: towards an affinity-based metalloproteinase profiling protocol.
A compound library of 96 enantiopure N-terminal succinyl hydroxamate functionalized peptides was synthesized on solid phase. All compounds were tested for their inhibitory potential towards MMP-9, MMP-12 and ADAM-17, which led to the identification of both broad spectrum inhibitors and metalloproteinase-selective ones. Eight potent and less potent inhibitors were immobilized on Sepharose beads and evaluated in solid-phase enrichment of active MMP-9, MMP-12 and ADAM-17. In addition, one of these inhibitors was used for solid-phase enrichment of endogenous ADAM-17 from a complex proteome (a lysate prepared from cultured A549 cells).
Geurink
Paul
P
Department of Bio-organic Synthesis (BioSyn), Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands.
Klein
Theo
T
Leeuwenburgh
Michiel
M
van der Marel
Gijs
G
Kauffman
Henk
H
Bischoff
Rainer
R
Overkleeft
Herman
H
D006877:Hydroxamic Acids / Q000737:chemistry* / Q000494:pharmacology; D045726:Metalloproteases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000145:classification; D015394:Molecular Structure; D019151:Peptide Library; D040081:Protein Array Analysis; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000145:classification
D006877:Hydroxamic Acids; D019151:Peptide Library; D011994:Recombinant Proteins; D045726:Metalloproteases