The present invention features a chemoselective ligation reaction that can be carried out under physiological conditions. In general, the invention involves condensation of a specifically engineered phosphine, which can provide for formation of an amide bond between the two reactive partners resulting in a final product comprising a phosphine moiety, or which can be engineered to comprise a cleavable linker so that a substituent of the phosphine is transferred to the azide, releasing an oxidized phosphine byproduct and producing a native amide bond in the final product. The selectivity of the reaction and its compatibility with aqueous environments provides for its application in vivo (e.g., on the cell surface or intracellularly) and in vitro (e.g., synthesis of peptides and other polymers, production of modified (e.g., labeled) amino acids).
本发明涉及一种可以在生理条件下进行的
化学选择性连接反应。一般来说,该发明涉及特定设计的膦化合物的缩合作用,该膦化合物可以提供两个反应物之间的酰胺键形成,从而产生一个包含膦基团的最终产物,或者可以被设计成包含可裂解的连接剂,使膦的取代基转移到
叠氮化合物上,释放出一个氧化膦副产物,并在最终产物中产生一个天然的酰胺键。该反应的选择性及其与
水性环境的兼容性使其可以应用于体内(例如在细胞表面或细胞内)和体外(例如合成肽和其他聚合物,生产改性(例如标记)
氨基酸)。