ACYLAMINO BORONIC ACIDS AND DIFLUOROBORANE ANALOGS OF AMINO-ACIDS - POTENT INHIBITORS OF CHYMOTRYPSIN AND ELASTASE
ACYLAMINO BORONIC ACIDS AND DIFLUOROBORANE ANALOGS OF AMINO-ACIDS - POTENT INHIBITORS OF CHYMOTRYPSIN AND ELASTASE
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DOI：
10.1021/jm00150a027
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发表时间：
1985-01-01
影响因子：
7.3
通讯作者：
KATZENELLENBOGEN, JA
中科院分区：
文献类型：
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作者：
KINDER, DH;KATZENELLENBOGEN, JA
通过硼酸盐同源反应制备了一系列1-酰氨基硼酸(IA-VA)，它们是苯丙氨酸、苯甘氨酸、丙氨酸、缬氨酸和异亮氨酸的类似物，作为丝氨酸蛋白酶α-糜蛋白酶和弹性蛋白酶的潜在过渡态抑制剂。与硼酸相比，用氢氟酸处理生成的二氟硼烷(IB-VB)更容易提纯。由于二氟硼烷在水中容易水解，它们被证明是制备硼酸的方便的前驱体。苯丙氨酸和苯甘氨酸类似物I和II是α-糜蛋白酶的良好竞争性抑制剂(Ki=0.3-8微米)，丙氨酸、缬氨酸和异亮氨酸类似物(III-IV)是弹性蛋白酶的良好抑制剂(Ki-0.1-35微米)。基于它们的高亲和力和硼酸形成硼酸盐络合物的倾向，这些酰氨基硼酸可能作为过渡态抑制剂发挥作用。
A series of 1-acylamino boronic acids (IA-VA), analogues of the amino acids phenylalanine, phenylglycine, alanine, valine, and isoleucine, were prepared as potential transition-state inhibitors of the serine proteases .alpha.-chymotrypsin and elastase, by a boronate homologation reaction. The corresponding difluoroboranes (IB-VB), produced from the boronic acids by treatment with HF, were more easily purified then the boronic acids. Since the difluoroboranes readily hydrolyze in water, they proved to be convenient precursors for the boronic acids. The phenylalanine and phenylglycine analogues I and II were good competitive inhibitors of .alpha.-chymotrypsin (Ki = 0.3-8 .mu.M), and the alanine, valine, and isoleucine analogues (III-IV) proved to be good inhibitors of elastase (Ki - 0.1-35 .mu.M). On the basis of their high affinity and the tendency of boronic acids to form borate complexes, these acylamino boronic acids may be behaving as transition-state inhibitors.