Chemical Synthesis of Highly Congested gp120 V1V2 N-Glycopeptide Antigens for Potential HIV-1-Directed Vaccines

被引：47

作者：

Aussedat, Baptiste ^{[1
]}

Vohra, Yusuf ^{[1
]}

Park, Peter K. ^{[1
]}

Fernandez-Tejada, Alberto ^{[1
]}

Alam, S. Munir ^{[3
]}

Dennison, S. Moses ^{[3
]}

Jaeger, Frederick H. ^{[3
]}

Anasti, Kara ^{[3
]}

Stewart, Shelley ^{[3
]}

Blinn, Julie H. ^{[3
]}

Liao, Hua-Xin ^{[3
,4
]}

Sodroski, Joseph G. ^{[6
,7
,8
,9
]}

Haynes, Barton F. ^{[3
,4
,5
]}

Danishefsky, Samuel J. ^{[1
,2
]}

机构：

[1] Sloan Kettering Inst Canc Res, Bioorgan Chem Lab, New York, NY 10065 USA

[2] Columbia Univ, Dept Chem, New York, NY 10027 USA

[3] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27710 USA

[4] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA

[5] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA

[6] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA

[7] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02215 USA

[8] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA

[9] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA 02139 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2013年 / 135卷 / 35期

关键词：

BETA-MANNOPYRANOSIDES; ANTIBODY; 2G12; NEUTRALIZING ANTIBODIES; GLYCAN RECOGNITION; HIGH-MANNOSE; CONVERGENT; HIV-1; GLYCOSYLATION; GLYCOPROTEIN; EPITOPE;

D O I：

10.1021/ja405990z

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Critical to the search for an effective HIV-1 vaccine is the development of immunogens capable of inducing broadly neutralizing antibodies (BnAbs). A key first step in this process is to design immunogens that can be recognized by known BnAbs. The monoclonal antibody PG9 is a BnAb that neutralizes diverse strains of HIV-1 by targeting a conserved carbohydrate protein epitope in the variable 1 and 2 (V1V2) region of the viral envelope. Important for recognition are two closely spaced N-glycans at Asn(160) and Asn(156). Glycopeptides containing this synthetically challenging bis-N-glycosylated motif were prepared by convergent assembly, and were shown to be antigenic for PG9. Synthetic glycopeptides such as these may be useful for the development of HIV-1 vaccines based on the envelope V1V2 BnAb epitope.

引用

页码：13113 / 13120

页数：8

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