Coyne C P, Smith J E, Keeton K
Department of Clinical Science, College of Veterinary Medicine, Kansas State University, Manhattan 66506.
Am J Vet Res. 1992 Nov;53(11):2058-66.
A selected group of pharmaceutical compounds were evaluated for the ability to inhibit the biochemical activity of fibrinoligase (coagulation factor XIIIa*) in pooled equine plasma. Criteria for the pharmaceuticals selected were based on the mechanism of the transglutamination biochemical reaction mediated by coagulation factor XIIa*. These criteria were complemented by recognition of the molecular configuration and chemical composition of amino acid residue side chains involved in the process of covalent fibrin monomer polymerization (cross-linking, transglutamination) mediated by this enzyme. Each pharmaceutical was evaluated individually and in combination with other potential coagulation factor XIIIa* inhibitors in an effort to detect additive and synergistic phenomenon. In this context, pharmaceuticals with a carbonylamide (eg, cefuroxime, Girard's reagent-P, prolinamide) were applied in concert with compounds with a terminal amine (eg, D-arginine, L-lysine) functional group. In concept, this method theoretically served to competitively simulate glutamine and lysine amino acid residues within strands of fibrin monomer substrate involved in phase I (carbonylamide) and phase II (terminal amine) of the transglutamination reaction (covalent fibrin monomer cross-linking). Halogen-dinitro and ethylene compounds were also evaluated because of their reported ability to inactivate enzyme systems dependent on an intact sulfhydryl group located at their biochemically active site (eg, cystine amino acid residue). This group of pharmaceutical compounds failed to inhibit the biochemical activity mediated by coagulation factor XIIIa* in equine plasma.
对一组选定的药物化合物进行了评估，以确定它们抑制马血浆中纤维蛋白连接酶（凝血因子XIIIa*）生化活性的能力。所选药物的标准基于凝血因子XIIa介导的转谷氨酰胺生化反应机制。这些标准通过识别参与该酶介导的共价纤维蛋白单体聚合（交联、转谷氨酰胺）过程的氨基酸残基侧链的分子构型和化学成分得到补充。每种药物都单独进行了评估，并与其他潜在的凝血因子XIIIa抑制剂联合评估，以检测相加和协同现象。在这种情况下，将含有羰基酰胺的药物（如头孢呋辛、吉拉德试剂-P、脯氨酰胺）与含有末端胺（如D-精氨酸、L-赖氨酸）官能团的化合物协同使用。从概念上讲，该方法理论上用于竞争性模拟参与转谷氨酰胺反应（共价纤维蛋白单体交联）第一阶段（羰基酰胺）和第二阶段（末端胺）的纤维蛋白单体底物链中的谷氨酰胺和赖氨酸氨基酸残基。还对卤素二硝基化合物和乙烯化合物进行了评估，因为据报道它们能够使依赖于位于其生化活性位点的完整巯基（如胱氨酸氨基酸残基）的酶系统失活。这组药物化合物未能抑制马血浆中凝血因子XIIIa*介导的生化活性。
