硅烷二醇肽拟肽对丝氨酸蛋白酶的抑制作用。
Serine protease inhibition by a silanediol peptidomimetic.
机构信息
Department of Chemistry, Temple University, 1901 North 13th Street, Philadelphia, Pennsylvania 19122, USA.
出版信息
Org Lett. 2012 Sep 7;14(17):4422-5. doi: 10.1021/ol301933n. Epub 2012 Aug 16.
Abstract
Silanediol peptidomimetics are demonstrated to inhibit a serine protease. Asymmetric synthesis of the inhibitor was accomplished using Brown hydroboration and CBS reduction of an acylsilane intermediate. The silanediol product was found to inhibit the serine protease chymotrypsin with a K(i) of 107 nM. Inhibition of the enzyme may involve exchange of a silane hydroxyl with the active site serine nucleophile, contrasting with previous silanediol protease inhibitors.
摘要
硅醇肽拟肽被证明可以抑制丝氨酸蛋白酶。通过布朗硼氢化和酰基硅烷中间体的 CBS 还原，实现了抑制剂的不对称合成。发现硅醇产物以 107 nM 的 K(i)抑制丝氨酸蛋白酶糜蛋白酶。酶的抑制作用可能涉及硅烷羟基与活性位点丝氨酸亲核试剂的交换，这与以前的硅醇肽蛋白酶抑制剂不同。
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