Courter Joel R, Abdo Mohannad, Brown Stephen P, Tucker Matthew J, Hochstrasser Robin M, Smith Amos B
Department of Chemistry, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
J Org Chem. 2014 Jan 17;79(2):759-68. doi: 10.1021/jo402680v. Epub 2013 Dec 20.
The design and synthesis of alanine-rich α-helical peptides constrained in a partially unfolded state by incorporation of the S,S-tetrazine phototrigger has been achieved, permitting, upon photochemical release, observation by 2D-IR spectroscopy of the subnanosecond conformational dynamics that govern the early steps associated with α-helix formation. Solid-phase peptide synthesis was employed to elaborate the requisite fragments, with full peptide construction via solution-phase fragment condensation. The fragment union tactic was also employed to construct (13)C═(18)O isotopically edited amides to permit direct observation of conformational motion at or near specific peptide bonds.
通过引入S,S-四嗪光触发剂，实现了设计和合成处于部分解折叠状态的富含丙氨酸的α-螺旋肽，在光化学释放后，可通过二维红外光谱观察亚纳秒级构象动力学，这些动力学控制着与α-螺旋形成相关的早期步骤。采用固相肽合成法制备所需片段，并通过溶液相片段缩合进行全肽构建。还采用片段连接策略构建了(13)C═(18)O同位素编辑的酰胺，以直接观察特定肽键处或其附近的构象运动。
