Purwin Maciej, Markowska Agnieszka, Bruzgo Irena, Rusak Tomasz, Surażyński Arkadiusz, Jaworowska Urszula, Midura-Nowaczek Krystyna
Department of Organic Chemistry, Medical University of Bialystok, Mickiewicza 2A Str, 15-222 Białystok, Poland.
Department of Physical Chemistry, Medical University of Bialystok, Mickiewicza 2A Str, 15-222 Białystok, Poland.
Int J Pept Res Ther. 2017;23(2):235-245. doi: 10.1007/s10989-016-9555-3. Epub 2016 Sep 19.
Fifteen new peptide derivatives of ɛ-aminocaproic acid (EACA) containing the known fragment -Ala-Phe-Lys- with an affinity for plasmin were synthesised in the present study. The synthesis was carried out a solid phase. The following compounds were synthesised: H-Phe-Lys-EACA-X, H-d-Ala-Phe-Lys-EACA-X, H-Ala-Phe-Lys-EACA-X, H-d-Ala-Phe-EACA-X and H-Ala-Phe-EACA-X, where X = OH, NH and NH-(CH)-NH. All peptides, except for those containing the sequence H-Ala-Phe-EACA-X, displayed higher inhibitory activity against plasmin than EACA. The most active and selective inhibitor of plasmin was the compound H-d-Ala-Phe-Lys-EACA-NH which inhibited the amidolytic activity of plasmin (IC = 0.02 mM), with the antifibrinolytic activity weaker than EACA. The resulting peptides did not affect the viability of fibroblast cells, colon cancer cell line DLD-1, breast MCF-7 and MDA-MB-231 cell lines.
在本研究中合成了15种含有已知片段-Ala-Phe-Lys-且对纤溶酶有亲和力的ε-氨基己酸（EACA）新肽衍生物。合成采用固相法进行。合成了以下化合物：H-Phe-Lys-EACA-X、H-d-Ala-Phe-Lys-EACA-X、H-Ala-Phe-Lys-EACA-X、H-d-Ala-Phe-EACA-X和H-Ala-Phe-EACA-X，其中X = OH、NH和NH-(CH)-NH。除了含有序列H-Ala-Phe-EACA-X的那些肽外，所有肽对纤溶酶的抑制活性均高于EACA。最具活性和选择性的纤溶酶抑制剂是化合物H-d-Ala-Phe-Lys-EACA-NH，它抑制纤溶酶的酰胺水解活性（IC = 0.02 mM），抗纤维蛋白溶解活性比EACA弱。所得肽不影响成纤维细胞、结肠癌细胞系DLD-1、乳腺癌MCF-7和MDA-MB-231细胞系的活力。
