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Systematic Synthesis and Binding Study of HIV V3 Glycopeptides Reveal the Fine Epitopes of Several Broadly Neutralizing Antibodies.

Abstract：

:A class of new glycan-reactive broadly neutralizing antibodies represented by PGT121, 10-1074, and PGT128 has recently been discovered that targets specific N-glycans and the peptide region around the V3 domain. However, the glycan specificity and fine epitopes of these bNAbs remain to be further defined. We report here a systematic chemoenzymatic synthesis of homogeneous V3 glycopeptides derived from the HIV-1 JR-FL strain carrying defined N-glycans at N332, N301, and N295 sites. Antibody binding studies revealed that both the nature and site of glycosylation in the context of the V3 domain were critical for high-affinity binding. It was found that antibody PGT128 exhibited specificity for high-mannose N-glycan with glycosylation site promiscuity, PGT121 showed binding specificity for glycopeptide carrying a sialylated N-glycan at N301 site, and 10-1074 was specific for glycopeptide carrying a high-mannose N-glycan at N332 site. The synthesis and binding studies permit a detailed assessment of the glycan specificity and the requirement of peptide in the context of antibody-antigen recognition. The identified glycopeptides can be used as potential templates for HIV vaccine design.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Orwenyo J,Cai H,Giddens J,Amin MN,Toonstra C,Wang LX

doi

10.1021/acschembio.7b00319

subject

Has Abstract

pub_date

2017-06-16 00:00:00

pages

1566-1575

issue

6

eissn

1554-8929

issn

1554-8937

journal_volume

12

pub_type

杂志文章

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