Hanglow A C, Lugo A, Walsky R, Visnick M, Coffey J W, Fotouhi N
Department of Inflammation, Hoffmann-La Roche Inc., Nutley, NJ 07110.
Biochem Biophys Res Commun. 1994 Dec 15;205(2):1156-63. doi: 10.1006/bbrc.1994.2787.
The tissue inhibitors of metalloproteinases (TIMPs) represent a family of naturally occurring protein inhibitors of stromelysin and other members of the family of matrix metalloproteinases. A series of peptides based on the N-terminal sequence of natural TIMP-1 was synthesized and assessed for inhibitory activity against purified human stromelysin. Inhibitor peptides were identified in the loop (bounded by the disulfide bonds [C3-C99] and [C13-C124]), e.g., [C3(Acm)-C13], (IC50, 42 microM). It was established that inhibition was due to the free sulfhydryl group of either C13 or C124. However, peptides within [C70(Acm)-C98(Acm)] inhibited stromelysin independently of zinc co-ordination by cysteine. The binding epitope in TIMP-1 may be discontinuous and comprised of sequences from at least 2 loops.
金属蛋白酶组织抑制剂（TIMPs）是一类天然存在的蛋白抑制剂，可抑制基质溶解素和基质金属蛋白酶家族的其他成员。基于天然TIMP-1的N端序列合成了一系列肽，并评估了它们对纯化的人基质溶解素的抑制活性。在环区（由二硫键[C3-C99]和[C13-C124]界定）中鉴定出了抑制肽，例如[C3(Acm)-C13]，（IC50为42微摩尔）。已确定抑制作用是由于C13或C124的游离巯基所致。然而，[C70(Acm)-C98(Acm)]内的肽可独立于半胱氨酸与锌的配位作用而抑制基质溶解素。TIMP-1中的结合表位可能是不连续的，且由至少2个环区的序列组成。
