Stachel S J, Hu H, Van Q N, Shaka A J, Van Vranken D L
Department of Chemistry, University of California-Irvine 92697-2025, USA.
Bioorg Med Chem. 1998 Sep;6(9):1439-46. doi: 10.1016/s0968-0896(98)00076-5.
Covalent crosslinks can control local peptide conformation. In tripeptide sequences of the general formula Cys-Xxx-Cys, cysteine disulfides have been previously shown to enforce a C7 equatorial gamma-turn conformation (also referred to as an inverse gamma-turn). Much less is known about the effects of dityrosine and ditryptophan crosslinks on local peptide structure. In a series of tripeptides, ditryptophan crosslinks were formed using the two-step process of acid-promoted Mannich dimerization followed by oxidative aromatization. In these peptides, with the general formula Trp-Xxx-Trp (Xxx not equal to Gly), ditryptophan crosslinks were found to stabilize a C7 equatorial gamma-turn conformation in DMSO-d6. Rigorous support for a C7 equatorial conformation in the crosslinked sequence Trp-Pro-Trp came from a variety of 1H NMR experiments and molecular modelling. Interproton distances were derived from NOE buildups that were determined through a series of double pulsed field gradient spin echo (DPFGSE) experiments. In addition, the small temperature dependence of the i+2 NH chemical shifts (delta delta/delta T < 2 ppm/degree C) provided further support for the intramolecular hydrogen bond which defines a gamma-turn.
共价交联可以控制局部肽构象。在通式为Cys-Xxx-Cys的三肽序列中，半胱氨酸二硫键先前已被证明可强制形成C7赤道γ-转角构象（也称为反向γ-转角）。关于二酪氨酸和二色氨酸交联对局部肽结构的影响，人们了解得要少得多。在一系列三肽中，通过酸促进的曼尼希二聚化然后氧化芳构化的两步过程形成二色氨酸交联。在这些通式为Trp-Xxx-Trp（Xxx不等于Gly）的肽中，发现二色氨酸交联在氘代二甲亚砜（DMSO-d6）中稳定了C7赤道γ-转角构象。对交联序列Trp-Pro-Trp中C7赤道构象的严格支持来自各种1H NMR实验和分子建模。质子间距离来自通过一系列双脉冲场梯度自旋回波（DPFGSE）实验确定的NOE积累。此外，i+2 NH化学位移的小温度依赖性（δδ/δT < 2 ppm/℃）为定义γ-转角的分子内氢键提供了进一步支持。
