Chemoproteomics (also known as chemical proteomics) entails a broad array of techniques used to identify and interrogate protein-small molecule interactions. Chemoproteomics complements phenotypic drug discovery, a paradigm that aims to discover lead compounds on the basis of alleviating a disease phenotype, as opposed to target-based drug discovery (reverse pharmacology), in which lead compounds are designed to interact with predetermined disease-driving biological targets. As phenotypic drug discovery assays do not provide confirmation of a compound's mechanism of action, chemoproteomics provides valuable follow-up strategies to narrow down potential targets and eventually validate a molecule's mechanism of action. Chemoproteomics also attempts to address the inherent challenge of drug promiscuity in small molecule drug discovery by analyzing protein-small molecule interactions on a proteome-wide scale. A major goal of chemoproteomics is to characterize the interactome of drug candidates to gain insight into mechanisms of off-target toxicity and polypharmacology.
Chemoproteomics assays can be stratified into three basic types. Solution-based approaches involve the use of drug analogs that chemically modify target proteins in solution, tagging them for identification. Immobilization-based approaches seek to isolate potential targets or ligands by anchoring their binding partners to an immobile support. Derivatization-free approaches aim to infer drug-target interactions by observing changes in protein stability or drug chromatography upon binding. Computational techniques complement the chemoproteomic toolkit as parallel lines of evidence supporting potential drug-target pairs, and are used to generate structural models that inform lead optimization. Several targets of high profile drugs have been identified using chemoproteomics, and the continued improvement of mass spectrometer sensitivity and chemical probe technology indicates that chemoproteomics will play a large role in future drug discovery.
Cette page est générée automatiquement et peut contenir des informations qui ne sont pas correctes, complètes, à jour ou pertinentes par rapport à votre recherche. Il en va de même pour toutes les autres pages de ce site. Veillez à vérifier les informations auprès des sources officielles de l'EPFL.
Une chimiothèque est une banque de données de molécules. Les chimiothèques peuvent contenir de plusieurs dizaines à plusieurs millions de composés chimiques. Selon leur contenu (chémotype, châssis moléculaire, diversité, , etc.), leur mode de stockage et leur provenance, il est possible de classer les chimiothèques en différentes catégories. On distingue, par exemple: les chimiothèques virtuelles, où les composés chimiques sont entreposés sous forme de données électroniques ; les chimiothèques focalisées sur un type de substance, lorsque le contenu ne se préoccupe que d’un espace chimique restreint.
La biologie chimique, ou chémobiologie, est une discipline scientifique qui étudie le vivant à l'aide d'outils chimiques. C'est la traduction de chemical biology, terme introduit en 1945 au California Institute of Technology (Caltech). À la traduction littérale « biologie chimique », on préfère aujourd'hui le terme « chémobiologie » qui bien que demeurant un domaine de recherche fondamentale, s'avère capable de conduire assez rapidemnt à des applications dans de nombreux domaines (santé, environnement, agrochimie, écologie, thérapeutique, diagnostic).
In the field of drug discovery, reverse pharmacology also known as target-based drug discovery (TDD), a hypothesis is first made that modulation of the activity of a specific protein target thought to be disease modifying will have beneficial therapeutic effects. Screening of chemical libraries of small molecules is then used to identify compounds that bind with high affinity to the target. The hits from these screens are then used as starting points for drug discovery.
We will cover key concepts of Medicinal Chemistry, from identification of active chemical starting points to how they are optimized to deliver drug candidates. We will use real case studies from the p
Closely interfacing with bioengineering and medicine, this course provides foundational concepts in applying small-molecule chemical toolsets to probe the functions of living systems at the mechanisti
Chemical biology is a key discipline in biomedical research for drug discovery, synthetic biology and protein functional annotation. We will give a broad perspective of the field ranging from seminal
Analyse l'activité et le développement de l'ATPase d'une enzyme mutante DDX3, couvrant les chaperons de l'ARN, les structures cristallines et le profilage des protéines à base de spectrométrie de masse.
Explore les méthodes de calcul pour prédire les mécanismes thérapeutiques de la COVID-19 par la réépuration des médicaments et l'apprentissage automatique.
Explore les méthodes de profilage protéomique, y compris les approches ABPP, MS et l'identification quantitative des cibles à l'aide de l'étiquetage SILAC et TMT.