Torrini I, Zecchini G P, Paglialunga Paradisi M, Lucente G, Gavuzzo E, Mazza F, Pochetti G, Traniello S, Spisani S, Cerichelli G
Dipartimento di Studi Farmaceutici, Università La Sapienza, Roma, Italy.
Biopolymers. 1994 Oct;34(10):1291-302. doi: 10.1002/bip.360341002.
For-Thp-Leu-delta ZPhe-OMe (2), an analogue of the chemotactic tripeptide For-Met-Leu-Phe-OMe, containing 4-aminotetrahydrothiopyran-4-carboxylic acid (Thp) and (Z)-2,3-didehydrophenylalanine (delta ZPhe) as achiral, conformationally restricted mimics of Met and Phe, respectively, has been synthesized. In the crystal the new formyltripeptide adopts a type I beta-turn conformation stabilized by a weak H bond between the formylic oxygen and the delta ZPhe NH. 1H-nmr analysis based on NH solvent accessibility and nuclear Overhauser effect experiments suggests that the beta-turn is not preferred in CDCl3 solution where a gamma-turn, centered at the Thp residue, prevails. The biological activity of 2 has been determined on human neutrophils and compared to that of previously studied analogues. The tripeptide 2 is practically unable to elicit superoxide anion production and lysozyme release, while slight, but not statistically significant activity was induced in chemotaxis. The role of the orientation of the aromatic ring with respect to the backbone adjacent atoms is discussed.
已合成了For-Thp-Leu-δZPhe-OMe（2），它是趋化性三肽For-Met-Leu-Phe-OMe的类似物，含有4-氨基四氢硫代吡喃-4-羧酸（Thp）和（Z）-2,3-二脱氢苯丙氨酸（δZPhe），分别作为Met和Phe的非手性、构象受限模拟物。在晶体中，新的甲酰基三肽采取I型β-转角构象，由甲酰基氧与δZPhe的NH之间的弱氢键稳定。基于NH溶剂可及性和核Overhauser效应实验的1H-核磁共振分析表明，在以Thp残基为中心的γ-转角占主导的CDCl3溶液中，β-转角并非首选构象。已测定了2对人中性粒细胞的生物活性，并与先前研究的类似物进行了比较。三肽2几乎无法引发超氧阴离子的产生和溶菌酶的释放，而在趋化性方面诱导了轻微但无统计学意义的活性。讨论了芳环相对于主链相邻原子的取向的作用。
