Carbohydrate-centered maleimide cluster as a new type of templates for multivalent peptide assembling. synthesis of multivalent HIV-1 gp41 peptides.
This paper describes a facile synthesis of carbohydrate-centered maleimide clusters and their application as a new type of templates for multivalent peptide assembling. Simultaneous introduction of multiple maleimide functionalities onto a carbohydrate core was achieved through the reaction of carbohydrate-based polyamines with methoxycarbonylmaleimide or with the N-hydroxylsuccinimide ester of 6-maleimidohexanoic acid. The clustered maleimides placed on the carbohydrate core allow rapid and highly chemoselective ligation with multiple copies of cysteine-containing peptides under virtually neutral conditions at room temperature. This mild and highly efficient ligation method is extremely valuable for synthesizing large and complex multivalent peptides that may not be easily obtained by conventional ligation methods. The usefulness of the maleimide clusters as a new type of templates for multivalent peptide synthesis was exemplified by the synthesis of two tetravalent gp41 peptides incorporating the sequence of the potent HIV inhibitor, T20. The synthetic multivalent gp41 peptides are useful as novel immunogens to raise specific antibodies for HIV studies. They are also useful probes for studying HIV membrane fusion mechanisms.
Wang
Lai-Xi
LX
Institute of Human Virology, University of Maryland Biotechnology Institute, University of Maryland, 725 W. Lombard Street, Baltimore 21201, USA. wangx@umbi.umd.edu
Ni
Jiahong
J
Singh
Suddham
S
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000737:chemistry; D002241:Carbohydrates / Q000737:chemistry*; D003545:Cysteine / Q000737:chemistry; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000235:genetics; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D008301:Maleimides / Q000737:chemistry*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics; D010455:Peptides / Q000138:chemical synthesis*
D019380:Anti-HIV Agents; D002241:Carbohydrates; D015700:HIV Envelope Protein gp41; D008301:Maleimides; D010446:Peptide Fragments; D010455:Peptides; D000077560:Enfuvirtide; D003545:Cysteine