Diaziridines Synthesis for Chemoselective

il y a 4 semaines


Grenoble, France Département de Chimie Moléculaire, CNRS - Université Grenoble Alpes Temps plein

**Diaziridines synthesis for chemoselective methionine bioconjugation**:

- Réf **ABG-126696**
- Stage master 2 / Ingénieur- Durée 6 mois- Salaire net mensuel approximately 600 euros- 06/11/2024- Département de Chimie Moléculaire, CNRS - Université Grenoble Alpes- Lieu de travail- Grenoble Auvergne-Rhône-Alpes France- Champs scientifiques- Chimie
- Mots clés- Organic Synthesis, Heterocyclic Compounds, Bioconjugation-
- 29/11/2024**Établissement recruteur**:
**Site web**:
This internship is proposed in the SeRCO team, dedicating its research activities to the development of new synthetic methods to access original molecules. Our synthetic targets are either complex natural products and analogues or bioactive molecules. Within the Département de Chimie Moléculaire the SeRCO team benefits state of the art equipements for research in organic chemistry and a stimulating research environment.

**Description**:
**Context**:

- Chemical modification of native amino acids (lysine, cysteine, and to a lesser extent tyrosine) is largely used for protein bioconjugation, however selectivity control is an issue. An emerging trend is to target less frequently occurring amino acids such as methionine (Met).[1] Met is naturally scare (2.5%) and its expression at specific positions on the surface of a protein is possible by site-directed mutagenesis.- The ReACT methodology, involving a chemoselective reaction of Met with oxaziridines has recently become a method of choice to target Met residues in protein bioconjugation.[2] However, it suffers from an unproductive_ O_-transfer pathway competing with the desired _N_-transfer. In this project, we propose to study the potential of diaziridines as sulfur imidation agents acting through selective _N_-transfer process.**Objectives**:

- The objective of the internship is to develop the synthesis of original diaziridines and to explore their potential in sulfur imidation reactions with the aim to develop new tools for the chemoselective bioconjugation of peptides / proteins containing at least one methionine residue. The reactivity of diaziridines with methionines will be investigated and compared to that of oxaziridines recently used in the ReACT (Redox Active Chemical Tagging) methodology. We will specifically target symmetrical diaziridines carrying an azide or alkyne function that will serve as a functional handle to conjugate proteins with various labels or biomolecules (carbohydrates, lipids) through click chemistry. Such selective transformations are expected to represent a new method to modulate the biological and physicochemical properties of proteins.- **Profil**:
He/she will be expected to acquire a good knowledge of the literature related to this project and to harness it for the benefits of the project.

**Prise de fonction**:

- 06/01/2025



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