Posted by: Footler PJ16 OCT 2013
For five years researchers at the University of Copenhagen have been working on new ways to manipulate proteins and peptides. Protein-based drugs, a rapidly growing class of pharmaceuticals, are already used to treat some serious conditions such as cancer, diabetes, leukaemias and sclerosis.
However, as proteins are large, intricate and fragile they can be difficult to work with under industrial conditions. Since their chemical make-up often closely resembles the body’s own chemical structures, the researchers believe that working with proteins under conditions nearer to those found in the human body could lead to cleaner and safer pharmaceuticals.
An example of this new “gentle” chemistry, involving readily available maleimides and N-hydroxylamines, was published as “Site-selective three component reaction for dual functionalization of peptides” in the journal Chemical Communications.
As well as the gentler approach the new method offers two advantages in that the reactions occur in a single one-pot synthesis and offer the possibility of attaching two so-called functional groups to individual proteins. For example, a polyethylene glycol (PEG) structure coupled to a protein (referred to as a PEGylated protein) offers a number of possible pharmaceutical applications. This process can be difficult to control but by dividing the PEG into shorter chains and attaching them to two sites on a protein, the medicinal effect becomes more predictable and easier to control, with potentially lowered risk of side effects.
Furthermore, being able to attach two functional groups on a single protein allows the synthesis of proteins with three functions, since the protein itself could serve as a function. For example, the researchers used their method to attach two molecular-imaging moieties to a tumour-binding cyclic peptide which could be used to help guide a surgeon to the tumour’s location.