title: Chemical synthesis of highly congested gp120 V1V2 N-glycopeptide antigens for potential HIV-1-directed vaccines.
abstract: 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.
authors.affiliation: Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10065, United States.
authors.forename: Baptiste
authors.initials: B
authors.lastname: Aussedat
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Vohra
authors.forename: Peter K
authors.initials: PK
authors.lastname: Park
authors.forename: Alberto
authors.initials: A
authors.lastname: Fernández-Tejada
authors.forename: S Munir
authors.initials: SM
authors.lastname: Alam
authors.forename: S Moses
authors.initials: SM
authors.lastname: Dennison
authors.forename: Frederick H
authors.initials: FH
authors.lastname: Jaeger
authors.forename: Kara
authors.initials: K
authors.lastname: Anasti
authors.forename: Shelley
authors.initials: S
authors.lastname: Stewart
authors.forename: Julie H
authors.initials: JH
authors.lastname: Blinn
authors.forename: Hua-Xin
authors.initials: HX
authors.lastname: Liao
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Sodroski
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Danishefsky
mesh_terms: D016915:AIDS Vaccines / Q000737:chemistry / Q000276:immunology*; D000941:Antigens / Q000737:chemistry / Q000276:immunology*; D002236:Carbohydrate Conformation; D018360:Crystallography, X-Ray; D006020:Glycopeptides / Q000737:chemistry / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D008958:Models, Molecular; D008969:Molecular Sequence Data
chemical_list: D016915:AIDS Vaccines; D000941:Antigens; D006020:Glycopeptides; D015699:HIV Envelope Protein gp120
references.citation: J Virol. 1996 Feb;70(2):1100-8
references.pmid: 8551569
references.citation: AIDS Res Hum Retroviruses. 1992 Aug;8(8):1459-60
references.pmid: 1466982
references.citation: Org Lett. 2001 Mar 22;3(6):851-4
references.pmid: 11263898
references.citation: Nature. 2011 Nov 23;480(7377):336-43
references.pmid: 22113616
references.citation: Biopolymers. 2010;94(4):373-84
references.pmid: 20593459
references.citation: Science. 1994 Nov 4;266(5186):776-9
references.pmid: 7973629
references.citation: J Am Chem Soc. 2004 Jun 2;126(21):6576-8
references.pmid: 15161285
references.citation: J Immunol. 2007 Apr 1;178(7):4424-35
references.pmid: 17372000
references.citation: Nature. 2011 Sep 22;477(7365):466-70
references.pmid: 21849977
references.citation: J Am Chem Soc. 2009 Apr 29;131(16):5792-9
references.pmid: 19341309
references.citation: Angew Chem Int Ed Engl. 2013 Jul 22;52(30):7646-65
references.pmid: 23775885
references.citation: PLoS One. 2012;7(8):e43903
references.pmid: 22928048
references.citation: Science. 2003 Jun 27;300(5628):2065-71
references.pmid: 12829775
references.citation: Chemistry. 2010 Nov 22;16(44):13163-75
references.pmid: 20878803
references.citation: Carbohydr Res. 1996 Jan 4;280(1):67-84
references.pmid: 8581896
references.citation: J Am Chem Soc. 2004 Aug 11;126(31):9560-2
references.pmid: 15291558
references.citation: Angew Chem Int Ed Engl. 2003 Jan 27;42(4):431-4
references.pmid: 12569509
references.citation: Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15684-9
references.pmid: 18838688
references.citation: J Am Chem Soc. 2007 Sep 12;129(36):11042-4
references.pmid: 17711286
references.citation: Angew Chem Int Ed Engl. 2005 Mar 4;44(11):1665-8
references.pmid: 15685675
references.citation: J Am Chem Soc. 2013 Mar 27;135(12):4700-3
references.pmid: 23461434
references.citation: Angew Chem Int Ed Engl. 2000 Oct 16;39(20):3652-3656
references.pmid: 11091428
references.citation: Proc Natl Acad Sci U S A. 2013 Mar 12;110(11):4351-6
references.pmid: 23426631
references.citation: J Med Chem. 2005 May 5;48(9):3126-9
references.pmid: 15857118
references.citation: Bioorg Med Chem Lett. 2004 May 3;14(9):2285-9
references.pmid: 15081026
references.citation: Angew Chem Int Ed Engl. 2012 Nov 12;51(46):11566-70
references.pmid: 22945377
references.citation: J Am Chem Soc. 2009 Nov 25;131(46):16669-71
references.pmid: 19886622
references.citation: J Virol. 2002 Jul;76(14):7293-305
references.pmid: 12072528
references.citation: J Virol. 2002 Jul;76(14):7306-21
references.pmid: 12072529
references.citation: Int J Pept Protein Res. 1992 Sep-Oct;40(3-4):294-9
references.pmid: 1478787
references.citation: J Am Chem Soc. 2012 Oct 3;134(39):16430-3
references.pmid: 22954207
references.citation: Science. 2009 Oct 9;326(5950):285-9
references.pmid: 19729618
references.citation: Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):12759-61
references.pmid: 8917491
references.citation: Angew Chem Int Ed Engl. 2004 May 3;43(19):2557-61
references.pmid: 15127452
references.citation: N Engl J Med. 2009 Dec 3;361(23):2209-20
references.pmid: 19843557
references.citation: Angew Chem Int Ed Engl. 2012 Nov 12;51(46):11571-5
references.pmid: 23011954
references.citation: Angew Chem Int Ed Engl. 2004 May 3;43(19):2562-5
references.pmid: 15127453
references.citation: J Org Chem. 1996 Jul 12;61(14):4506-4507
references.pmid: 11667369
references.citation: J Virol. 2011 Oct;85(19):9998-10009
references.pmid: 21795340
references.citation: J Am Chem Soc. 2001 Jun 20;123(24):5826-8
references.pmid: 11403627
references.citation: Nat Struct Mol Biol. 2013 Jul;20(7):804-13
references.pmid: 23708607
references.citation: Curr Opin Chem Biol. 1999 Dec;3(6):643-9
references.pmid: 10600722
references.citation: Nat Chem Biol. 2013 Aug;9(8):521-6
references.pmid: 23831758
references.citation: Proc Natl Acad Sci U S A. 2012 Nov 20;109(47):E3268-77
references.pmid: 23115339
references.citation: Nat Biotechnol. 2012 May 07;30(5):423-33
references.pmid: 22565972
references.citation: J Virol. 2010 Oct;84(20):10510-21
references.pmid: 20686044