A New Highly Versatile Handle for Chemistry on a Solid Support: The Pipecolic Linker

Abstract

The versatility of the pipecolic linker (Pip-linker) is illustrated by the synthesis of modified amino acids, C-terminal-modified pseudopeptides, and cyclic peptides, through side-chain anchoring of a lysine residue (see figure). Introduction of the first residue was easily accomplished and the Pip-linker revealed to be robust enough to support various chemical modifications.

Total synthesis of cyclic heptapeptide Rolloamide B

“…In 2010, four of the 60 peptide drugs on the market reached global sales in excess of US $ 1 billion, and more than 500 peptides are under clinical development. 12,13 The topology of macrocyclic peptides reduces their susceptibility to attack by exo-and endo-peptidases; 14,15 thus, they play an important role in nature and are attractive targets for drug discovery and biomedical research. [16][17][18][19][20] Well-known examples of cyclic peptide drugs include the natural antibiotic vancomycin, hormone oxytocin, neuropeptide vasopressin and antibiotics cyclosporine and tyrocidine A.…”