Protein engineering

Walk On The Wild Side

Protein engineering is a fascinating science in which you "play around" with your molecule to better undersand it and improve on it. Through rational chemical and biocomputerized protein design, it involves, structure-activity relationship (SAR) and folding studies, protein interaction and recognition, labelling and immobilization, profiling and optimization. 

Top of page

Synthesis

Automated solid phase and liquid phase synthesis of peptides residues using Boc or Fmoc chemistry, even above 60 residues. Our platform allows for cost-effective production from mg to gram amounts.

Purities > 98% can be reached after HPLC purification and MS structural confirmation.

Side-chain modifications or unusual amino acids can be used, and protein folding is performed routinely with control of the disulfide pattern. 

Top of page

Labelling

The development of our Isotope Dilution Assay strategies has stimulated the development of several strategies for site-directed or uniform labelling of peptides and proteins with stable isotopes such as 13-C, D or 15-N (labelled amino acids). This is performed through solid phase peptide synthesis, recombinant protein expression systems using controlled growth media or semi-synthesis.

Top of page

Modifications

In addition to solid phase peptide synthesis and refolding, we also use liquid phase chemistry to specifically modify or label free amino acids or polypeptidic structures. Site-directed chemical labelling and photoaffinity labelling of fluorescent dyes are routinely performed to study reactive sites, and the label can be directed towards specific reactive sites.

Top of page

Profiling & optimization

Finding analogues of a lead compound that have improved efficiency, selectivity, stability, solubility or reduced toxicity is crucial in early-stage drug development program. To perform structure-function investigations, alanine scanning and other types of modifications and residue mutations are performed in large series at analytical scale. In some cases, we also take in charge automated parallel synthesis, manual synthesis, as well as site-directed mutation strategies in recombinant expression systems.

For lead compound optimization, we also like to look at how Nature has done it. So we have developed original biocomputing tools to screen for analogues of a lead compounds designed by Nature. This is extremely useful to identify the important regions of a molecular backbone and often provides original ideas for the design of new analogues.

All these strategies are based on our long-standing understanding of the characteristics of amino acids in a peptidic chain. This, together with computer-assisted modelisation and matching for homologies against protein and DNA sequence databases, facilitates the identification of essential residues.

Top of page

Protein-ligand interaction

We have also developed and validated original strategies for covalent and non-covalent interactions with proteins. We use mass spectrometry with soft ionization combined to proprietary affinity-based techniques for the identification, characterization and evaluation of ligands.

Top of page