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Multimerized HIV‐gp41‐derived peptides as fusion inhibitors and vaccines
Author(s) -
Nomura Wataru,
Mizuguchi Takaaki,
Tamamura Hirokazu
Publication year - 2016
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.22782
Subject(s) - trimer , gp41 , heptad repeat , chemistry , peptide , lipid bilayer fusion , antigen , isoleucine , antiserum , monomer , stereochemistry , biochemistry , combinatorial chemistry , peptide sequence , amino acid , leucine , epitope , membrane , biology , dimer , immunology , organic chemistry , gene , polymer
ABSTRACT To date, several antigens based on the amino‐terminal leucine/isoleucine heptad repeat (NHR) region of an HIV‐1 envelope protein gp41 and fusion inhibitors based on the carboxy‐terminal leucine/isoleucine heptad repeat (CHR) region of gp41 have been reported. We have developed a synthetic antigen targeting the membrane‐fusion mechanism of HIV‐1. This uses a template designed with C3‐symmetric linkers and mimics the trimeric form of the NHR‐derived peptide N36. The antiserum obtained by immunization of the N36 trimeric antigen binds preferentially to the N36 trimer and blocks HIV‐1 infection effectively, compared with the antiserum obtained by immunization of the N36 monomer. Using another template designed with different C3‐symmetric linkers, we have also developed a synthetic peptide mimicking the trimeric form of the CHR‐derived peptide C34, with ∼100 times the inhibitory activity against the HIV‐1 fusion mechanism than that of the monomer C34 peptide. A dimeric derivative of C34 has potent inhibitory activity at almost the same levels as this C34 trimer mimic, suggesting that presence of a dimeric form of C34 is structurally critical for fusion inhibitors. As examples of rising mid‐size drugs, this review describes an effective strategy for the design of HIV vaccines and fusion inhibitors based on a relationship with the native structure of proteins involved in HIV fusion mechanisms. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 622–628, 2016.