Detection and quantitative analysis of two independent binding modes of a small ligand responsible for DC-SIGN clustering
Articolo
Data di Pubblicazione:
2016
Citazione:
Detection and quantitative analysis of two independent binding modes of a small ligand responsible for DC-SIGN clustering / C. Guzzi, P. Alfarano, I. Sutkeviciute, S. Sattin, R. Ribeiro Viana, F. Fieschi, A. Bernardi, J. Weiser, J. Rojo, J. Angulo, P.M. Nieto. - In: ORGANIC & BIOMOLECULAR CHEMISTRY. - ISSN 1477-0520. - 14:1(2016), pp. 335-344. [10.1039/C5OB02025E]
Abstract:
DC-SIGN (dendritic cell-specific ICAM-3 grabbing non-integrin) is a C-type lectin receptor (CLR) 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-SIGNdependent
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.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
C. Guzzi, P. Alfarano, I. Sutkeviciute, S. Sattin, R. Ribeiro Viana, F. Fieschi, A. Bernardi, J. Weiser, J. Rojo, J. Angulo, P.M. Nieto
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