A new tri-orthogonal strategy for peptide cyclization.
A solid phase tri-orthogonal protection/cleavage strategy that uses acidic, basic, and neutral conditions is described. Strategically protected alpha-azido-gamma-9-fluorenylmethyl-L-glutamate (1) and alpha-azido-epsilon-N-Fmoc-L-lysine (2) were incorporated into growing peptides on Wang resin using a novel azide protection strategy. These residues, separated by 1-3 monomers, were deprotected at the side chains and cyclized via lactam formation. The N-terminus was further functionalized to extend the chain. This method represents a straightforward protocol for peptide cyclization on solid support.
Lundquist
Joseph T
JT
Division of Discovery Chemistry, Wyeth Research, Collegeville, Pennsylvania 19426, USA. Lundquj@WAR.Wyeth.com
Pelletier
Jeffrey C
JC
D000596:Amino Acids; D001665:Binding Sites; D002384:Catalysis; D003432:Cross-Linking Reagents; D003500:Cyclization; D010455:Peptides / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000138:chemical synthesis*; D011487:Protein Conformation
D000596:Amino Acids; D003432:Cross-Linking Reagents; D010455:Peptides; D010456:Peptides, Cyclic