Stürzebecher J, Stürzebecher U, Markwardt F
Toxicon. 1986;24(6):585-95. doi: 10.1016/0041-0101(86)90179-0.
Benzamidine derivatives which are competitive inhibitors of trypsin-like serine proteinases also inhibited the enzymatic activity of batroxobin, a thrombin-like snake venom proteinase. Structure-activity relationships showed that primary amides of 4-amidinophenyl-alpha-aminobutyric acid have pronounced, relatively selective antibatroxobin activity. Identical effects were found on batroxobin isolated from the venoms of Bothrops atrox or Bothrops moojeni. Esters containing a benzamidine moiety acylated the active centre serine hydroxyl of either batroxobin, however, the inhibition was temporary. Such compounds, especially 4-amidinophenyl esters of substituted benzoic acids, are a particularly useful tool for designing acyl-batroxobin intermediates with different deacylation rates. With 4-nitrophenyl 4'-guanidinobenzoate, the acyl enzyme was formed so rapidly that titration of the active site of batroxobin was possible. Irreversible inhibition of batroxobin was caused only by the selective thrombin inhibitor D-Phe-Pro-ArgCH2Cl.
作为胰蛋白酶样丝氨酸蛋白酶竞争性抑制剂的苯甲脒衍生物，也能抑制类凝血酶蛇毒蛋白酶——巴曲酶的酶活性。构效关系表明，4-脒基苯基-α-氨基丁酸的伯酰胺具有显著的、相对选择性的抗巴曲酶活性。从矛头蝮或莫氏矛头蝮蛇毒中分离得到的巴曲酶也有相同的效果。含有苯甲脒部分的酯酰化了巴曲酶的活性中心丝氨酸羟基，然而，这种抑制是暂时的。这类化合物，尤其是取代苯甲酸的4-脒基苯酯，是设计具有不同脱酰化速率的酰基巴曲酶中间体的特别有用的工具。对于4-硝基苯基4'-胍基苯甲酸酯，酰基酶形成得非常迅速，以至于可以对巴曲酶的活性位点进行滴定。只有选择性凝血酶抑制剂D-Phe-Pro-ArgCH2Cl能引起巴曲酶的不可逆抑制。
