Developing biocatalytic methodologies for glycosylation of therapeutic peptides and proteins

Antimicrobial resistance, the prevalence of diabetes and multidrug resistance in cancer are important challenges faced today. However, therapeutic peptides and proteins could provide solutions, as they have relevant and vast drug potential. Although their native forms are limited by poor pharmacokinetic properties, modifying their structures with attached sugars (glycosylation) can remove this deficit.
Controllable chemical glycosylation of peptides and proteins is synthetically challenging, involving multistep synthesis and use of protecting groups. Chemical methods can involve vast stoichiometric reagent use, rare-metal catalysts, harsh conditions and toxic materials. Current bio-based methods, like recombinant technologies and glycosyltransferase (enzyme) use, have their own challenges, such as difficulty controlling product glycosylation and poor synthetic application, respectively.

This proposal's premise is to develop novel chemo-enzymatic glycosylation methodologies for the late-stage homogeneous functionalization of therapeutic peptides and proteins. These new methodologies will be more facile to apply than current enzyme techniques, greener than current chemical routes and more tailorable than recombinant technologies. The goal is a new, controllable glycosylation methodology that is easy to apply and more sustainable, meeting 11 of the 12 principles of green chemistry.