Aussedat Baptiste, Vohra Yusuf, Park Peter K, Fernández-Tejada Alberto, Alam S Munir, Dennison S Moses, Jaeger Frederick H, Anasti Kara, Stewart Shelley, Blinn Julie H, Liao Hua-Xin, Sodroski Joseph G, Haynes Barton F, Danishefsky Samuel J
Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10065, United States.
J Am Chem Soc. 2013 Sep 4;135(35):13113-20. doi: 10.1021/ja405990z. Epub 2013 Aug 22.
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.
寻找有效的HIV-1疫苗的关键在于开发能够诱导广泛中和抗体（BnAbs）的免疫原。这一过程的关键第一步是设计能够被已知BnAbs识别的免疫原。单克隆抗体PG9是一种BnAb，它通过靶向病毒包膜可变区1和2（V1V2）中保守的碳水化合物-蛋白质表位来中和多种HIV-1毒株。对于识别至关重要的是Asn(160)和Asn(156)处两个紧密相邻的N-聚糖。通过汇聚组装制备了含有这种合成具有挑战性的双N-糖基化基序的糖肽，并证明其对PG9具有抗原性。这样的合成糖肽可能有助于基于包膜V1V2 BnAb表位开发HIV-1疫苗。
