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).
STATEMENT AS TO FEDERALLY SPONSORED RESEARCH
This invention was made, at least in part, with a government grant from the National Institutes of Health (Grant Nos. NIH grant GM58867-01), the Office of Naval Research (Grant No. N00014-98-0605), and the Department of Energy (Order No. N00014-98-F-0402, Contract No. DE-AC03-76SF00098). The U.S. government may have certain rights in this invention.