There is a growing interest in using peptides as drugs as they can often bind very strongly to targets, have low toxicity, and can influence certain biological processes in the body that traditional small molecule medicines cannot. A major challenge with designing peptide drugs is that they are often unable to cross the membrane and reach targets within cells.  This is because cell membranes are fatty, whereas peptides prefer to be transported in water.  While some naturally occurring peptides can travel through membranes and previous studies have highlighted some important features that facilitate this, there are no hard and fast rules.

Last year, CIPPS Partner Investigator Professor David Baker, and his colleague Assistant Professor Gaurav Bhardwaj, both from the University of Washington led an exciting study, with contributions from CIPPS director Professor David Craik and his group, into creating peptides that can travel through membranes. The team first designed a wide range of peptides with different features expected to aid in membrane crossing, including features that would help the peptide interact with fatty substances rather than water. They then used computational modelling followed by experimental characterisation and animal studies to evaluate their designs. The team produced a range of peptides that could enter cells after being swallowed by animals, highlighting an important new strategy and necessary features for peptide drug design. This work was published in the high-impact journal Cell (IF 66.85), and has led to a new spin-out company Vilya, Inc., with ARCH Venture Partners, of which PI David Baker and Gaurav Bhardwaj are co-founders.

Reference:

https://www.sciencedirect.com/science/article/pii/S0092867422009229?via%3Dihub