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Dissecting Key Multivalent Processes in Glycosidase Inhibition: Insights from Thermodynamic Modelling and Atomistic Simulations

Title: Dissecting Key Multivalent Processes in Glycosidase Inhibition: Insights from Thermodynamic Modelling and Atomistic Simulations
Authors: Spichty, Martin; Liang, Yan; Schettini, Rosaria; Izzo, Irene; Bodlenner, Anne; Compain, Philippe
Contributors: Laboratoire d'innovation moléculaire et applications (LIMA); Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS); Università degli Studi di Salerno = University of Salerno (UNISA); Université de Strasbourg
Source: https://hal.science/hal-04325646 ; 2023.
Publisher Information: CCSD
Publication Year: 2023
Subject Terms: multivalency multivalent inhibitory effect thermodynamic modelling molecular dynamics; multivalency; multivalent inhibitory effect; thermodynamic modelling; molecular dynamics; [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry
Description: Multivalency represents a powerful approach to increase the inhibition potency of moderate glycosidase inhibitors. Regarding the key role of catalytic glycoside hydrolysis in biology, understanding the molecular mechanisms and origin of the multivalent inhibitory effect is of great interest and presents a fascinating playground for theoretical studies. Our teams have recently dissected key processes of multivalent glycosidase inhibition through the use of different neoglycoclusters based on deoxynojirimycin (DNJ) inhitopes and a cyclopeptoid scaffold. This companion article details the theoretical aspects of this former study. A thermodynamic model is developed and validated, compared to literature, and extended to account for particularities of the charged DNJ inhitopes.
Document Type: report
Language: English
Relation: BIORXIV: 2023.11.29.569169
DOI: 10.1101/2023.11.29.569169
Availability: https://hal.science/hal-04325646; https://hal.science/hal-04325646v1/document; https://hal.science/hal-04325646v1/file/Spichty_Multivalency_Uploaded.pdf; https://doi.org/10.1101/2023.11.29.569169
Rights: info:eu-repo/semantics/OpenAccess
Accession Number: edsbas.7A64336A
Database: BASE