Selective and facile cyclization of N-chloroacetylated peptides from the C4 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. Chim. Acta 1989; 72, 857-867). The use of Li salts in an organic solvent to influence cyclization of a reactive peptide that only polymerizes in an aqueous solvent, has not been reported. Here, the selective and facile cyclization 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 stoichiometric 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 and these were confirmed using reversed-phase HPLC and mass spectrometric analyses 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 amphipathic peptides may be useful in many situations beyond those described here.
Robey
F A
FA
Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA. frobey@dir.nidcr.nih.gov
D000107:Acetylation; D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D003500:Cyclization; D004126:Dimethylformamide / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D015699:HIV Envelope Protein gp120 / Q000737:chemistry*; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D018021:Lithium Chloride / Q000737:chemistry*; D013058:Mass Spectrometry; D008956:Models, Chemical; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry*
D015699:HIV Envelope Protein gp120; D010446:Peptide Fragments; D004126:Dimethylformamide; D018021:Lithium Chloride