Ph-D :Artificial DNAzyme for asymmetric oxidations

19 Mar 2024
Job Information

Organisation/Company

Univ. Grenoble Alpes

Department

Chimie Biologie Santé

Research Field

Chemistry » Organic chemistry

Researcher Profile

First Stage Researcher (R1)

Country

France

Application Deadline

12 Apr 2024 - 23:00 (Europe/Paris)

Type of Contract

Temporary

Job Status

Full-time

Hours Per Week

35

Offer Starting Date

1 Oct 2024

Is the job funded through the EU Research Framework Programme?

Not funded by an EU programme

Reference Number

ANR-17-EURE-0003

Is the Job related to staff position within a Research Infrastructure?

No

Offer Description

A key area for industry is the development of new catalysts for the synthesis of chiral molecules.1 Thanks to their high catalytic efficiency and compatibility with aqueous solvents, biocatalysts,2 which are natural or modified enzymes, are particularly interesting for the development of more environmentally-friendly processes. However, there are limits linked to the protein nature of the chiral auxiliary. Proteins can become irreversibly denatured under certain conditions (heating, co-solvents, etc.), making them more difficult to use and causing storage problems. In addition, they are generally manufactured by biological processes that may be subject to contamination.

The use of nucleic acids as chiral auxiliaries represents an interesting alternative. They can be produced chemically, and while the three-dimensional structures they form (eg. duplexes) are also sensitive to denaturation, this is reversible. The use of double-stranded DNA for various asymmetric transformations has been shown to be possible.3–6 The use of G4-quadruplex (G4) structures,7 based on the stacking of guanine tetrads for asymmetric catalysis, has recently attracted interest.8–11 One of the feature of these structures is that a single DNA sequence can adopt several G4 topologies (conformations) that are in equilibrium with each other.

In asymmetric catalysis, these different topologies lead to different efficiencies and orientations,12 demonstrating that controlling the conformation of G4 is crucial. This can be achieved by immobilizing guanine-rich oligonucleotides on a peptide template to create mimics of a specific G4 topology.13,14

We have shown that these mimes can catalyze the enantioselective oxidation of thioethers in combination with a copper II complex.15 However, this enantioselective transformation competes with racemic sulfoxidation, which occurs outside G4. In addition, the enantiomer obtained depends mainly on the G4 region where the reaction occurs.

The thesis project aims to overcome these limitations by conjugating the metal complex to a precise region of the G4 mime. This strategy should make it possible to (i) prevent the reaction from occurring outside G4, (ii) control the orientation of the reaction by controlling the site where it takes place, and (iii) open up other enantioselective oxidation transformations such as olefin epoxidation.

Bibliography: 1              C. A. Busacca, D. R. Fandrick, J. J. Song and C. H. Senanayake, Adv. Synth. Catal., 2011, 353, 1825–1864.

2              J.-M. Choi, S.-S. Han and H.-S. Kim, Biotechnol. Adv., 2015, 33, 1443–1454. 3 G. Roelfes and B. L. Feringa, Angew. Chem. Int. Ed., 2005, 44, 3230–3232. 4                D. Coquière, B. L. Feringa and G. Roelfes, Angew. Chem. Int. Ed., 2007, 46, 9308–9311. 5              A. Rioz-Martínez, J. Oelerich, N. Ségaud and G. Roelfes, Angew. Chem. Int. Ed., 2016, 55, 14136–14140. 6          A. J. Boersma, B. L. Feringa and G. Roelfes, Angew. Chem. Int. Ed., 2009, 48, 3346–3348. 7                S. Burge, G. N. Parkinson, P. Hazel, A. K. Todd and S. Neidle, Nucleic Acids Res., 2006, 34, 5402–5415. 8         S. Roe, D. J. Ritson, T. Garner, M. Searle and J. E. Moses, Chem. Commun., 2010, 46, 4309–4311. 9          L.-X. Wang, J.-F. Xiang and Y.-L. Tang, Adv. Synth. Catal., 2015, 357, 13–20. 10              J. H. Yum, S. Park and H. Sugiyama, Org. Biomol. Chem., 2019, 17, 9547–9561. 11        M. Cheng, Y. Li, J. Zhou, G. Jia, S.-M. Lu, Y. Yang and C. Li, Chem. Commun., 2016, 52, 9644–9647. 12         C. Wang, G. Jia, Y. Li, S. Zhang and C. Li, Chem. Commun., 2013, 49, 11161–11163. 13   P. Murat, D. Cressend, N. Spinelli, A. Van der Heyden, P. Labbe, P. Dumy and E. Defrancq, ChemBioChem, 2008, 9, 2588–2591. 14 R. Bonnet, T. Lavergne, B. Gennaro, N. Spinelli and E. Defrancq, Chem. Commun., 2015, 51, 4850–3. 15         Y. Colas, S. Ménage, C. Marchi-Delapierre and N. Spinelli, ChemCatChem, 2023, n/a, e202300914.

Requirements

Research Field

Chemistry » Organic chemistry

Education Level

Master Degree or equivalent

Skills/Qualifications

The candidate should have a good university degree with a background in organic and bioorganic chemistry. Knowledge of (bio)inorganic chemistry would be appreciated.

Languages

ENGLISH

Level

Good

Languages

FRENCH

Level

Basic

Research Field

Chemistry » Organic chemistry

Years of Research Experience

None

Additional Information
Benefits

- Publications

- Congress

- Technical learning.

 

Eligibility criteria

Good academic results.

Selection process
Two candidates will be selected and the choice will be defined after an oral presentation in front of a jury.
Work Location(s)

Number of offers available

1

Company/Institute

Département de chimie moléculaire

Country

France

State/Province

Rhone-Alpes-Auvergne

City

Grenoble

Postal Code

38058

Street

570 rue de la chimie

Geofield

Number of offers available

1

Company/Institute

LCBM

Country

France

State/Province

Rhone-Alpes-Auvergne

City

Grenoble

Postal Code

38 054

Street

17 avenue des Martyrs

Geofield

Where to apply

E-mail

[email protected]

Contact

City

Saint-Martin-d'Hères

Website

https://www.univ-grenoble-alpes.fr/english/
https://dcm.univ-grenoble-alpes.fr/research/ingenierie-et-interactions-biomoleculaires
https://grad-chembiohealth.univ-grenoble-alpes.fr/

Street

621 avenue Centrale

Postal Code

38400

STATUS: EXPIRED