Metal-Free, Regioselective Triazole Ligations that Deliver Locked cis Peptide Mimetics

摘要

Chemical ligation reactions have become popular during recent years as they enable formation of chemoselective linkages under mild, often aqueous reaction conditions, and with high yields. Chemical ligations are especially useful if they can couple complex functionalized molecules without protecting groups under physiological conditions or in the presence of living cells. Reversible ligations have been used successfully in fragment-based screening and drug discovery. A ligation strategy furnishing conformationally locked, biologically active molecules would be an exciting extension of current methodology. Such a strategy could be especially valuable for the structure-based design and synthesis of inhibitors of protein-protein interactions and peptidyl iso-merases.