STD NMR study of the interactions between antibody 2G12 and synthetic oligomannosides that mimic selected branches of gp120 glycans

Enríquez-Navas, Pedro M, Chiodo, Fabrizio, Marradi, Marco, Angulo, Jesús ORCID: https://orcid.org/0000-0001-7250-5639 and Penadés, Soledad (2012) STD NMR study of the interactions between antibody 2G12 and synthetic oligomannosides that mimic selected branches of gp120 glycans. ChemBioChem, 13 (9). pp. 1357-1365. ISSN 1439-4227

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Abstract

The human immunodeficiency virus type-1 (HIV-1) is able to shield immunogenic peptide epitopes on its envelope spike (a trimer of two glycoproteins, gp120 and gp41) by presenting numerous host-derived N-linked glycans. Nevertheless, broadly neutralizing antibodies against gp120 and gp41 have been isolated from HIV-1-infected patients and provide protection against viral challenge in animal models. Among these, the monoclonal antibody 2G12 binds to clusters of high-mannose-type glycans that are present on the surface of gp120. These types of glycans have thus been envisaged as target structures for the development of synthetic agents capable of eliciting 2G12-like antibodies. High-resolution structural studies of 2G12 and chemically defined glycan-type ligands, including crystallographic data, have been performed to gain an insight into this interaction. Further studies are still required to design a carbohydrate-based vaccine for HIV. Our previous NMR studies highlighted different recognition modes of two branched synthetic oligosaccharides, a penta- and a heptamannoside, by 2G12 in solution. In order to clarify the underlying structural reasons for such different behaviors, we have herein "dissected" the branches into the linear tri- and tetra- oligomannosides by chemical synthesis and studied their interactions with 2G12 in solution by saturation transfer difference (STD) NMR spectroscopy. The results confirm the distinct preferences of 2G12 for the studied branches and afford explanations for the observed differences. This study provides important structural information for further ligand optimizations. Possible effects of structural modifications on the solvent-exposed end of the ligands are also discussed.

Item Type:	Article
Additional Information:	Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Uncontrolled Keywords:	antibodies, monoclonal,hiv envelope protein gp120,humans,oligosaccharides,microarray analysis,polysaccharides,biomimetic materials,magnetic resonance spectroscopy,sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Science > School of Pharmacy (former - to 2024)
UEA Research Groups:	Faculty of Science > Research Groups > Drug Delivery and Pharmaceutical Materials (former - to 2017) Faculty of Science > Research Groups > Pharmaceutical Materials and Soft Matter
Depositing User:	Pure Connector
Date Deposited:	21 Oct 2013 19:50
Last Modified:	24 Sep 2024 10:42
URI:	https://ueaeprints.uea.ac.uk/id/eprint/43762
DOI:	10.1002/cbic.201200119

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