Inhibition of matrix metalloproteinases by peptidyl hydroxamic acids.
Inhibition of matrix metalloproteinases by peptidyl hydroxamic acids.
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肽基异羟肟酸对基质金属蛋白酶的抑制。
DOI：
10.1006/bbrc.1994.1392
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发表时间：
1994
影响因子：
3.1
通讯作者：
Yutaka Nagai
中科院分区：
文献类型：
--
作者：
S. Odake;Y. Morita;T. Morikawa;N. Yoshida;Hisae Hori;Yutaka Nagai
间质胶原酶的合成抑制剂，三肽基和四肽基异羟肟酸，已被开发和测试其对人基质金属蛋白酶的抑制活性。水溶性抑制剂p-NH 2-Bz-Gly-Pro-D-Leu-D-Ala-NHOH（FN-439）可抑制间质和粒细胞胶原酶、粒细胞明胶酶和皮肤成纤维细胞基质溶解酶，IC 50分别为1 × 10 - 6 M、3.0 × 10 - 5 M和1.5 × 10 - 4，但不抑制嗜热菌蛋白酶和丝氨酸蛋白酶。发现FN-439即使在与链霉蛋白酶或人粒细胞弹性蛋白酶长时间孵育后仍保留其对基质金属蛋白酶的抑制活性，这表明FN-439是调节体内金属蛋白酶活性的抑制剂的优选候选物。
Synthetic inhibitors of interstitial collagenase, tri- and tetrapeptidyl hydroxamic acids, have been developed and tested for their inhibitory activities against human matrix metalloproteinases. A water soluble inhibitor, p-NH2-Bz-Gly-Pro-D-Leu-D-Ala-NHOH (FN-439) inhibited interstitial and granulocyte collagenases, granulocyte gelatinase and skin fibroblast stromelysin with IC50 of 1 x 10(-6) M, 3.0 x 10(-5) M and 1.5 x 10(-4), respectively, but not thermolysin and serine proteinases. FN-439 was found to retain its inhibitory activity against matrix metalloproteinases even after prolonged incubation with pronase or human granulocyte elastase, indicating a favorite candidate of the inhibitor to modulate metalloproteinase activities in vivo.