Dipartimento di Scienze del Farmaco, Università di Chieti-Pescara G. d'Annunzio, Via dei Vestini 31, 66100 Chieti, Italy.
J Pept Sci. 2012 Jun;18(6):418-26. doi: 10.1002/psc.2414. Epub 2012 Apr 24.
In the present study, we report synthesis and biological evaluation of the N-Boc-protected tripeptides 4a-l and N-For protected tripeptides 5a-l as new For-Met-Leu-Phe-OMe (fMLF-OMe) analogues. All the new ligands are characterized by the C-terminal Phe residue variously substituted at position 4 of the aromatic ring. The agonism of 5a-l and the antagonism of 4a-l (chemotaxis, superoxide anion production, lysozyme release as well as receptor binding affinity) have been examined on human neutrophils. No synthesized compounds has higher activity than the standard fMLF-OMe tripeptide to stimulate chemotaxis, although compounds 5a and 5c with -CH(3) and -C(CH(3))(3), respectively, in position 4 on the aromatic ring, are better than the standard tripeptide to stimulate the production of superoxide anion, in higher concentration. Compounds 4f and 4i, containing -F and -I in position 4, respectively, on the aromatic ring of phenylalanine, exhibit significant chemotactic antagonism. The influence of the different substitution at the position 4 on the aromatic ring of phenylalanine is discussed.
在本研究中，我们报告了 N-Boc 保护的三肽 4a-l 和 N-For 保护的三肽 5a-l 的合成及生物学评价，它们是新的 For-Met-Leu-Phe-OMe（fMLF-OMe）类似物。所有的新配体均具有 C 末端 Phe 残基，其芳环的第 4 位被各种取代。我们检测了 5a-l 的激动作用和 4a-l 的拮抗作用（趋化作用、超氧阴离子产生、溶菌酶释放以及受体结合亲和力）对人嗜中性粒细胞的影响。虽然化合物 5a 和 5c 在芳环的第 4 位上分别有-CH(3)和-C(CH(3))(3)取代，在刺激超氧阴离子产生方面优于标准三肽，但没有一种合成化合物的活性比标准 fMLF-OMe 三肽更高，以刺激趋化作用。在较高浓度下，化合物 5a 和 5c 对超氧阴离子的产生具有更好的刺激作用。化合物 4f 和 4i 含有 -F 和 -I，分别在芳环的第 4 位取代苯丙氨酸，表现出显著的趋化作用拮抗作用。讨论了苯丙氨酸芳环第 4 位不同取代对其的影响。
