Geurink Paul, Klein Theo, Leeuwenburgh Michiel, van der Marel Gijs, Kauffman Henk, Bischoff Rainer, Overkleeft Herman
Department of Bio-organic Synthesis (BioSyn), Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands.
Org Biomol Chem. 2008 Apr 7;6(7):1244-50. doi: 10.1039/b718352f. Epub 2008 Feb 22.
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).
在固相上合成了一个包含96种对映体纯的N-末端琥珀酰氧肟酸官能化肽的化合物库。测试了所有化合物对MMP-9、MMP-12和ADAM-17的抑制潜力，从而鉴定出了广谱抑制剂和金属蛋白酶选择性抑制剂。将8种强效和低效抑制剂固定在琼脂糖珠上，并在活性MMP-9、MMP-12和ADAM-17的固相富集实验中进行评估。此外，其中一种抑制剂被用于从复杂蛋白质组（由培养的A549细胞制备的裂解物）中固相富集内源性ADAM-17。
