Selective and facile cyclization of N-chloroacetylated peptides from the C-4 domain of HIV Gp120 in LiCl/DMF solvent systems

Lithium salts have been reported to mediate the solubilization of peptides in organic solvents in 1989 (Seebach, D., Thaler, A. & Beck. A. K. Helv. Ch im. Acta 1989; 72, 857-867). The use of Li salts in an organic solvent to i nfluence cyclization of a reactive peptide that only polymerizes in an aque ous solvent, has not been reported. Here, the selective and facile cyclizat ion of N-chloroacetylated, C-cysteine amide peptides from the C4 domain of HIV-1 gp120 in LiCl/DMF solvent systems is demonstrated. The addition of st oichiometric amounts of Tris base to 1 mg/mL peptide in LiCl/DMF solutions was sufficient to drive the cyclization to completion within 3 h at ambient temperatures. Cyclic peptides were the only detectable reaction products a nd these were confirmed using reversed-phase HPLC and mass spectrometric an alyses of the final products. In aqueous solutions at pH 7.4, only polymers were obtained as judged by HPLC and SDS-PAGE. The method of using Li salts in an organic solvent to enhance the cyclization of unprotected amphipathi c peptides may be useful in many situations beyond those described here.