Laudano A P, Doolittle R F
Proc Natl Acad Sci U S A. 1978 Jul;75(7):3085-9. doi: 10.1073/pnas.75.7.3085.
A series of small peptides corresponding to the amino termini of the fibrin alpha- and beta-chains has been synthesized. The peptides glycyl-L-prolyl-L-arginyl-L-proline and glycyl-L-prolyl-L-arginylsarcosine are potent inhibitors of fibrin polymerization. Moreover, these peptides have a natural stability stemming from their inherent resistance to proteolysis because of the involvement of amino acids in each of their peptide bonds. The peptide glycyl-L-prolyl-L-arginyl-L-proline binds to fibrinogen and to fragment D, in both cases with an association constant of approximately 5 x 10(4); it does not bind to fragment E. The number of binding sites is two for fibrinogen and one for fragment D. The tripeptide glycyl-L-prolyl-L-arginine binds less tightly and is less than half as effective in preventing polymerization. The peptide glycyl-L-histidyl-L-arginyl-L-proline, which corresponds exactly to the amino terminus of the fibrin beta-chain, does not inhibit the aggregation of fibrin monomers under the conditions used. It does bind weakly to fibrinogen, however, suggesting the involvement of sites other than those binding the alpha-chain analogues. Various other peptides were found not to inhibit polymerization; these included glycine-L-proline, L-prolyl-L-arginine and glycyl-L-prolyl-L-seryl-L-proline. The last-named corresponds to the serine/arginine amino acid replacement previously reported for a defective human fibrinogen.
已合成了一系列与血纤蛋白α链和β链氨基末端相对应的小肽。甘氨酰-L-脯氨酰-L-精氨酰-L-脯氨酸和甘氨酰-L-脯氨酰-L-精氨酰肌氨酸这两种肽是血纤蛋白聚合的有效抑制剂。此外，由于这些肽的每个肽键中的氨基酸参与其中，它们具有固有的抗蛋白水解能力，因而具有天然稳定性。甘氨酰-L-脯氨酰-L-精氨酰-L-脯氨酸肽与血纤蛋白原和D片段结合，在这两种情况下，其缔合常数约为5×10⁴；它不与E片段结合。血纤蛋白原的结合位点数量为两个，D片段的结合位点数量为一个。三肽甘氨酰-L-脯氨酰-L-精氨酸结合较弱，在阻止聚合方面的效果不到一半。与血纤蛋白β链氨基末端完全对应的甘氨酰-L-组氨酰-L-精氨酰-L-脯氨酸肽，在所使用的条件下不抑制血纤蛋白单体的聚集。然而，它确实与血纤蛋白原弱结合，这表明除了与α链类似物结合的位点外，还有其他位点参与。发现各种其他肽不抑制聚合；这些肽包括甘氨酸-L-脯氨酸、L-脯氨酰-L-精氨酸和甘氨酰-L-脯氨酰-L-丝氨酰-L-脯氨酸。最后一种肽对应于先前报道的有缺陷的人血纤蛋白原中的丝氨酸/精氨酸氨基酸替代。
