Design and synthesis of a template-assembled oligomannose cluster as an epitope mimic for human HIV-neutralizing antibody 2G12

被引:57
作者
Li, HG [1 ]
Wang, LX [1 ]
机构
[1] Univ Maryland, Inst Biotechnol, Inst Human Virol, Baltimore, MD 21201 USA
关键词
D O I
10.1039/b314565d
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
The synthesis and antibody-binding affinity of a novel template-assembled oligomannose cluster as an epitope mimic for human anti-HIV antibody 2G12 are described. Cholic acid was chosen as the scaffold and three high-mannose type oligosaccharide (Man(9)GlcNAc(2)Asn) moieties were selectively attached at the 3alpha, 7alpha, and 12alpha-positions of the scaffold through a series of regioselective transformations. Binding studies revealed that the synthetic oligosaccharide cluster is 46-fold more effective than the subunit Man(9)GlcNAc(2)Asn in inhibiting 2G12-binding to immobilized gp 120. The scaffold approach described in this paper provides an avenue to designing more effective epitope mimics for antibody 2G12 in the hope of developing a carbohydrate-based vaccine against HIV-1.
引用
收藏
页码:483 / 488
页数:6
相关论文
共 20 条
[1]   EFFICIENT NEUTRALIZATION OF PRIMARY ISOLATES OF HIV-1 BY A RECOMBINANT HUMAN MONOCLONAL-ANTIBODY [J].
BURTON, DR ;
PYATI, J ;
KODURI, R ;
SHARP, SJ ;
THORNTON, GB ;
PARREN, PWHI ;
SAWYER, LSW ;
HENDRY, RM ;
DUNLOP, N ;
NARA, PL ;
LAMACCHIA, M ;
GARRATTY, E ;
STIEHM, ER ;
BRYSON, YJ ;
CAO, YZ ;
MOORE, JP ;
HO, DD ;
BARBAS, CF .
SCIENCE, 1994, 266 (5187) :1024-1027
[2]   Antibodies, viruses and vaccines [J].
Burton, DR .
NATURE REVIEWS IMMUNOLOGY, 2002, 2 (09) :706-713
[3]   Antibody domain exchange is an immunological solution to carbohydrate cluster recognition [J].
Calarese, DA ;
Scanlan, CN ;
Zwick, MB ;
Deechongkit, S ;
Mimura, Y ;
Kunert, R ;
Zhu, P ;
Wormald, MR ;
Stanfield, RL ;
Roux, KH ;
Kelly, JW ;
Rudd, PM ;
Dwek, RA ;
Katinger, H ;
Burton, DR ;
Wilson, IA .
SCIENCE, 2003, 300 (5628) :2065-2071
[4]   The consequence of passive administration of an anti-human immunodeficiency virus type 1 neutralizing monoclonal antibody before challenge of chimpanzees with a primary virus isolate [J].
Conley, AJ ;
Kessler, JA ;
Boots, LJ ;
McKenna, PM ;
Schleif, WA ;
Emini, EA ;
Mark, GE ;
Katinger, H ;
Cobb, EK ;
Lunceford, SM ;
Rouse, SR ;
Murthy, KK .
JOURNAL OF VIROLOGY, 1996, 70 (10) :6751-6758
[5]   A NEW REAGENT WHICH MAY BE USED TO INTRODUCE SULFHYDRYL-GROUPS INTO PROTEINS, AND ITS USE IN THE PREPARATION OF CONJUGATES FOR IMMUNOASSAY [J].
DUNCAN, RJS ;
WESTON, PD ;
WRIGGLESWORTH, R .
ANALYTICAL BIOCHEMISTRY, 1983, 132 (01) :68-73
[6]   Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody [J].
Kwong, PD ;
Wyatt, R ;
Robinson, J ;
Sweet, RW ;
Sodroski, J ;
Hendrickson, WA .
NATURE, 1998, 393 (6686) :648-659
[7]   Cholic acid as template for multivalent peptide assembly [J].
Li, HG ;
Wang, LX .
ORGANIC & BIOMOLECULAR CHEMISTRY, 2003, 1 (20) :3507-3513
[8]  
LIS H, 1978, J BIOL CHEM, V253, P3468
[9]   Fine definition of the epitope on the gp41 glycoprotein of human immunodeficiency virus type 1 for the neutralizing monoclonal antibody 2F5 [J].
Parker, CE ;
Deterding, LJ ;
Hager-Braun, C ;
Binley, JM ;
Schülke, N ;
Katinger, H ;
Moore, JP ;
Tomer, KB .
JOURNAL OF VIROLOGY, 2001, 75 (22) :10906-10911
[10]   RECOGNITION PROPERTIES OF A PANEL OF HUMAN RECOMBINANT FAB FRAGMENTS TO THE CD4 BINDING-SITE OF GP120 THAT SHOW DIFFERING ABILITIES TO NEUTRALIZE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 [J].
ROBEN, P ;
MOORE, JP ;
THALI, M ;
SODROSKI, J ;
BARBAS, CF ;
BURTON, DR .
JOURNAL OF VIROLOGY, 1994, 68 (08) :4821-4828