Toniolo C, Bonora G M, Freer R J, Kennedy S P, Pittenger K L, Becker E L
C.N.R., Department of Organic Chemistry, University of Padova, Italy.
Peptides. 1988 Nov-Dec;9(6):1195-205. doi: 10.1016/0196-9781(88)90183-0.
The two diastereomeric sulphoxides and the sulphone derived from the formyl-methionyl tripeptide chemoattractant CHO-L-Met-L-Phe-OMe have been synthesized and fully characterized. The diastereomeric sulphoxide tripeptides have been separated at the stage of their N-tert-butyloxycarbonyl synthetic precursors. All of the oxidized sulphur derivatives induce secretion of granule enzymes with ED50s from 1-2 x 10(-9) M with no significant differences in activity among them. They are also active to the same relative extent in inducing chemotaxis. In parallel, a solution conformational analysis has been performed in solvents of widely different polarities and capabilities of H-bond formation using circular dichroism, infrared absorption and 1H nuclear magnetic resonance. No significant propensity for formation of intramolecularly (C = O...H-N) H-bonded folded forms has been detected in any of the four tripeptides. Intermolecular S = O...H-N interactions are postulated to tentatively explain the 1H nuclear magnetic resonance behavior of the Met and, particularly, Leu NH resonances of the two sulphoxide tripeptides in CDCl3 solution. The biological and conformational data agree with the recently proposed model of the chemotactic peptide receptor of rabbit neurotrophils, which involves the extended backbone of the integrity of the Met side-chain sulphide sulphur atom as a corollary point of ligand interaction.
已合成并全面表征了源自甲酰甲硫氨酰三肽趋化因子CHO-L-甲硫氨酸-L-苯丙氨酸-OMe的两种非对映体亚砜以及砜。非对映体亚砜三肽在其N-叔丁氧羰基合成前体阶段已被分离。所有氧化的硫衍生物均能诱导颗粒酶分泌，其半数有效剂量（ED50）为1 - 2×10⁻⁹ M，它们之间的活性无显著差异。它们在诱导趋化性方面也具有相同程度的活性。同时，使用圆二色性、红外吸收和¹H核磁共振在极性和形成氢键能力差异很大的溶剂中进行了溶液构象分析。在这四种三肽中，均未检测到形成分子内（C = O...H-N）氢键折叠形式的明显倾向。推测分子间S = O...H-N相互作用可初步解释在CDCl₃溶液中两种亚砜三肽的甲硫氨酸以及特别是亮氨酸NH共振的¹H核磁共振行为。生物学和构象数据与最近提出的兔嗜中性粒细胞趋化肽受体模型一致，该模型涉及甲硫氨酸侧链硫化物硫原子完整性的伸展主链作为配体相互作用的一个必然要点。
