Wayment Adam X, Johnson Nye C, Moreno Mariur Rodriguez, Stewart Christopher, Felix Braxton M, Lambert Isaac, Traynor Sarah A, Nielson P Michael, Lofgreen Grant Q, Smith Shannon L, Newton Madison P, Tretbar Jordan W, Nygaard Joseph M L, Harrell Kylie G, Kinghorn Michael J, Michaelis David J
Department of Chemsitry and Biochemistry, Brigham Young University, Provo, UT, USA.
Tetrahedron Lett. 2024 Apr 28;140. doi: 10.1016/j.tetlet.2024.155010. Epub 2024 Mar 29.
We report that squaric esters can serve as bifunctional reagents for selective peptide stapling reactions. Formation of the squaric amide staple occurs under mild conditions with amine-containing side chains. We show that short resin-bound peptides are readily stapled on solid phase and that stapling can occur at various relative positions along the peptide and with various amine tether lengths (e.g. Lysine, ornithine, etc). The squaric amide staples are stable to strong acid conditions used to cleave the stapled peptide from the resin and the stapled peptides show an increase in helicity as analyzed through circular dichroism.
我们报道了方酸酯可作为用于选择性肽环化反应的双功能试剂。方酸酰胺环化物在温和条件下与含胺侧链发生反应而形成。我们表明，短的树脂结合肽很容易在固相上进行环化，并且环化可以在肽链上的不同相对位置以及不同胺连接长度（例如赖氨酸、鸟氨酸等）下发生。方酸酰胺环化物对用于从树脂上裂解环化肽的强酸条件稳定，并且通过圆二色性分析表明，环化肽的螺旋度增加。
