Solid-phase synthesis of succinylhydroxamate peptides: functionalized matrix metalloproteinase inhibitors.
[reaction: see text] A novel solid-phase synthesis strategy toward succinylhydroxamate peptides, using an appropriately protected hydroxamate building block, is described. Rapid and efficient access is gained to amine-functionalized peptides, which can be decorated with, for instance, a fluorescent label. In addition, we demonstrate an on-resin synthesis of a biotinylated photoactivatable hydroxamate peptide, which can be used as an activity-based probe for matrix metalloproteinases and ADAMs.
Leeuwenburgh
Michiel A
MA
Department of Bio-organic Synthesis, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
Geurink
Paul P
PP
Klein
Theo
T
Kauffman
Henk F
HF
van der Marel
Gijs A
GA
Bischoff
Rainer
R
Overkleeft
Herman S
HS
D051722:ADAM Proteins / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D005456:Fluorescent Dyes / Q000737:chemistry; D006877:Hydroxamic Acids / Q000138:chemical synthesis*; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis*; D013386:Succinates / Q000138:chemical synthesis*
D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D006877:Hydroxamic Acids; D010455:Peptides; D013386:Succinates; D051722:ADAM Proteins; D008666:Metalloendopeptidases