Stabilizing proteins by methionine selective cross-linking

DossierGOCH.KIEM.KGC03.036
StatusLopend
Startdatum1 mei 2023
Einddatum30 april 2024
RegelingKIEM GoChem 2019-2024
Thema's
  • Bètatechniek
  • Sleuteltechnologieën - Chemische technologieën
  • Maatschappelijk Verdienvermogen - Valideren, doorontwikkelen en toepassen van strategieën
  • Gezondheid en Welzijn
  • Sleuteltechnologieën en duurzame materialen

Proteins are nature-derived molecules that have found wide applications in biotechnology, pharmaceuticals and biocatalysis. A major limitation for the use of proteins in such applications is their lack of stability. This is due to the disruption of the tertiary structure of a protein, which is responsible for the function of a protein. Earlier studies have shown that three cysteine residues, which are strategically incorporated in the sequence, can be crosslinked with a tris-electrophile. This so-called in situ cyclization of proteins (INCYPRO) results in the rigidification of the protein structure and ultimately higher stability of the protein. For some proteins, it would be beneficial to use another amino acid residue for modification as cysteine residues can be important for the function of a protein, e.g. as disulfide bridges or as active sites residues.
In this project, we will develop crosslinkers that are selective for methionine residues. Although these amino acids contribute to the function of proteins in biological systems, they are less important for the molecular function of proteins, thus making them suitable for crosslinking of proteins. Our plan is to first develop a set of trisfunctionalized crosslinkers that selectively react with the thioether functional group of methionine. Next, we will investigate the crosslinking conditions on the model protein (KIX domain) as a proof of concept. In the final step, we would like to prove that the function of the protein is retained by crosslinking the transpeptidase enzyme sortase A.

Contactinformatie

Maastricht University

Jordy Saya, contactpersoon
Telefoon: +31630061859

Consortiumpartners

bij aanvang project
  • Incircular B.V.