Tools
Tools
Guzzi, Cinzia, Alfarano, Pietro, Sutkeviciute, Ieva, Sattin, Sara, Ribeiro-viana, Renato, Fieschi, F., Bernardi, Anna, Weiser, Jorg, Rojo, J., Angulo, Jesus 
ORCID: https://orcid.org/0000-0001-7250-5639 and Nieto, Pedro M.
(2016)
Detection and quantitative analysis of two independent binding modes of a small ligand responsible for DC-SIGN clustering.
Organic & Biomolecular Chemistry, 14 (1).
pp. 335-344.
ISSN 1477-0520
Preview |
PDF (c5ob02025e(1))
- Accepted Version
Download (5MB) | Preview |
Abstract
DC-SIGN (dendritic cell-specific ICAM-3 grabbing non-integrin) is a C-type lectin receptor (CLRs) present, mainly in dendritic cells (DCs), as one of the major pattern recognition receptors (PRRs). This receptor has a relevant role in viral infection processes. Recent approaches aiming to block DC-SIGN have been presented as attractive anti-HIV strategies. DC-SIGN binds mannose or fucose-containing carbohydrates from viral proteins such as the HIV envelope glycoprotein gp120. We have previously demonstrated that multivalent dendrons bearing multiple copies of glycomimetic ligands were able to inhibit DC-SIGN-dependent HIV infection in cervical explant models. Optimization of glycomimetic ligands requires detailed characterization and analysis of their binding modes because they notably influence binding affinities. In a previous study we characterized the binding mode of DC-SIGN with ligand 1, which shows a single binding mode as demonstrated by NMR and X-ray crystallography. In this work we report the binding studies of DC-SIGN with pseudotrisaccharide 2, which has a larger affinity. Their binding was analysed by TR-NOESY and STD NMR experiments, combined with the CORCEMA-ST protocol and molecular modelling. These studies demonstrate that in solution the complex cannot be explained by a single binding mode. We describe the ensemble of ligand bound modes that best fit the experimental data and explain the higher inhibition values found for ligand 2
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | 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 |
| Related URLs: | |
| Depositing User: | Pure Connector |
| Date Deposited: | 19 Dec 2015 07:19 |
| Last Modified: | 29 Oct 2024 00:40 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/55800 |
| DOI: | 10.1039/C5OB02025E |
Downloads
Downloads per month over past year
Actions (login required)
 |
View Item |