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

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• 作者：Baptiste Aussedat ; Yusuf Vohra ; Peter K. Park ; Alberto Fern谩ndez-Tejada ; S. Munir Alam ; S. Moses Dennison ; Frederick H. Jaeger ; Kara Anasti ; Shelley Stewart ; Julie H. Blinn ; Hua-Xin Liao ; Joseph G. Sodroski ; Barton F. Haynes ; Samuel J. Danishefsky
• 刊名：Journal of the American Chemical Society
• 出版年：2013
• 出版时间：September 4, 2013
• 年：2013
• 卷：135
• 期：35
• 页码：13113-13120
• 全文大小：481K
• 年卷期：v.135,no.35(September 4, 2013)
• ISSN：1520-5126

文摘

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鈥損rotein epitope in the variable 1 and 2 (V1V2) region of the viral envelope. Important for recognition are two closely spaced N-glycans at Asn¹⁶⁰ and Asn¹⁵⁶. 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.