H2020Индивидуална стипендия2022–2024

GLYCOMIMIC · Gaining insights into Enzymes Transition States: Superacid as new tool to design specific CAZymes inhibitors.

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2022-09-01 → 2024-08-31
Финансиране от ЕС: 184 708 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Ензимите, които изграждат и разграждат въглехидратите, се изучават чрез стабилизиране на техните краткотрайни междинни състояния с помощта на суперкиселини. Познаването на тези структури помага за създаването на по-прецизни лекарства, като например антивирусни или антидиабетични препарати.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Gaining insights into Enzymes Transition States: Superacid as new tool to design specific CAZymes inhibitors.

Glycosciences study the structural and functional roles of carbohydrates in biology and have an increasing impact on many areas of our economy (health, food, natural resources). Carbohydrate Active enZymes (CAZymes), which catalyse the assembly (Glycosyl transferases, GTs) and breakdown (Glycosidases, GHs) of glycosidic linkage in carbohydrates, are essential to life, being involved in key cell functions. Their pharmacological modulation by means of selective CAZymes’ inhibitors can also have multiple applications (e.g. antiviral TamifluTM, antidiabetic GlysetTM, molecular chaperone GalafoldTM). The mechanism of the glycosylation reaction is believed to involve a species with substantial oxocarbenium ion character as reactive intermediate (glycosyl cations). Because of the chemical environment within the sugar ring, the stability and lifetime of the oxocarbenium ions in solutions are very low. The extreme reactivity of these cations has thus precluded for decades their direct observation and characterization in the deprotected form. Understanding the structure, conformation, reactivity, and interactions of glycosyl cations is essential to predict the outcome of glycosylation and to design selective inhibitors of CAZymes. In this context, GLYCOMIMIC general scientific objective was to develop an innovative superacid-based approach to gain insights into CAZymes’ transition states (glycosyl cations). Non-nucleophilic superacids, which constitute a powerful tool to take snapshots of transient superelectrophilic cations in solution, were used at this aim to generate and stabilize “naked” glycosyl cations. Our approach was developed across 3 work-packages (WP1 to WP3).

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Glycosciences study the structural and functional roles of carbohydrates in biology and have an increasing impact on many areas of our economy (health, food, natural resources). Carbohydrate Active enZymes (CAZymes), which catalyse the assembly (Glycosyl transferases, GTs) and breakdown (Glycosidases, GHs) of glycosidic linkage in carbohydrates, are essential to life, being involved in key cell functions. Their pharmacological modulation by means of selective CAZymes’ inhibitors can have multiple applications (e.g. antiviral TamifluTM, antidiabetic GlysetTM, molecular chaperone GalafoldTM). However, the design of inhibitors endowed of high selectivity is challenging, representing the major obstacle in discovering new potent and safe therapeutic agents targeting CAZymes. In this context, GLYCOMIMIC offers an innovative approach based on superacid chemistry to gain insights into CAZymes’ transition states (TS) and to help the design of specific inhibitors, paving the way for short-term impact on drug discovery! Superacid chemistry is only mastered by very few research groups in the world and is a European specificity of the Institute of Chemistry of Poitiers (IC2MP - UMR CNRS 7285 – France) and will be applied for the first time to glycosciences. With Univ. Barcelona (world leader in computer simulation of biological processes at atomic-electronic detail) acting as secondment, GLYCOMIMIC blends multidisciplinary states of the art research training in carbohydrate chemistry, superacids, low-temperature NMR analysis, DFT calculations, QM/MM dynamic simulation of enzymes and enzyme inhibition studies. It will provide a prolific fellow with an internationally competitive training, with the aim of advancing the career of an autonomous scientist in the EU and the next generation of multidisciplinary researchers in (bio)pharmaceutical sciences.

Оригинален текст от CORDIS (на английски).

Участници

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS · ParisКоординаторФранция