Design and synthesis of rhamnose-modified exenatide conjugate by sortase A-mediated ligation

AbstractExenatide modified with rhamnose as a hapten was designed and synthesized by Sortase A-mediated ligation. An Exenatide peptide analog comprised of 46 amino acids, including the sortase A recognition motif LPETG at the C-terminus, was synthesized by solid phase peptide synthesis method. A tri-glycine modified-rhamnose derivative was chemically synthesized in seven steps in good yield. The site-specific conjugation between them catalyzed by Sortase A completed in 3 h and the rhamnose-modified Exenatide conjugate was obtained after semi-preparative HPLC purification and characterized by MALDI-TOF MS. This method should be generally useful for the synthesis of other Exenatide analog for biological studies.