Hanglow A C, Lugo A, Walsky R, Finch-Arietta M, Lusch L, Visnick M, Fotouhi N
Department of Arthritis Research, Hoffmann-La Roche, Nutley, NJ 07110.
Agents Actions. 1993;39 Spec No:C148-50. doi: 10.1007/BF01972749.
Prostromelysin, a member of the family of matrix metalloproteinases, is secreted as a zymogen which is activated after cleavage of the His81-Phe82 bond. The 82 amino acid propeptide that is removed during activation contains 12 amino acids, MRKPRC75GVPDVG, that are highly conserved in all MMPs. We evaluated a series of peptides that span this region for their ability to inhibit stromelysin. The hexapeptide, Ac-RCGVPD, and the pentapeptide, Ac-RCGVP had IC50 values of approx. 10 microM. The tetrapeptide, Ac-RCGV, was somewhat less potent with an IC50 of 60 microM. Smaller peptides, e.g. Ac-RCG, were significantly less potent as inhibitors. Substitutions of Cys75 with Ser resulted in a complete loss of inhibitory activity. The peptides in this series also inhibited human fibroblast collagenase.
前基质溶解素是基质金属蛋白酶家族的一员，它以酶原形式分泌，在His81 - Phe82键断裂后被激活。在激活过程中被去除的82个氨基酸的前肽包含12个氨基酸，MRKPRC75GVPDVG，这些氨基酸在所有基质金属蛋白酶中高度保守。我们评估了一系列跨越该区域的肽抑制基质溶解素的能力。六肽Ac - RCGVPD和五肽Ac - RCGVP的IC50值约为10微摩尔。四肽Ac - RCGV的效力稍低，IC50为60微摩尔。更小的肽，如Ac - RCG，作为抑制剂的效力显著更低。将Cys75替换为Ser会导致抑制活性完全丧失。该系列中的肽也抑制人成纤维细胞胶原酶。
