It was a privilege to attend the 5th Annual Peptides Congress in London yesterday and interact with so many experts in this field. Here are some of my highlights:
Professor David Craik (apparently commonly mistaken for James Bond actor Daniel Craig) gave a fascinating presentation on cyclotides – cyclic peptides produced by a variety of plants. These peptides, comprising three disulphide bonds that form a “knot”, are both varied and robust. Prof. Craik provided an overview of these peptides and their utility as a backbone for the delivery of therapeutic peptide epitopes. The peptides are capable of surviving the digestive system, making oral delivery of peptide drugs a genuine possibility, although currently the bioavailability of such orally-administered peptides is low.
A potential solution to the low bioavailability of orally-administered peptide drugs was provided by Mohamed ElSayed (Eli Lilly and Co.) who provided an eloquent discussion of the challenges in the oral delivery of structurally diverse therapeutic peptides. One of the current strategies presented was the enteric coating of a peptide formulation combined with a peptidase inhibitors (e.g. citric acid, which creates a low pH microenvironment to delay the action of proteases, such as trypsin) and permeation enhancers (e.g. caprylic acid, which disrupts tight-junctions between gut cells).
The generation of new highly selective peptide-based drugs is being addressed by Bicycle Therapeutics Ltd and Liuhong Chen provided insights into the exciting development of Bicycle peptides. These bicycle-shaped peptides can be produced in chemically-constrained phage-display libraries, which enables the selection of peptides with high target specificity. Conjugation of the peptides to imaging agents enables high-contrast, tissue-selective imaging. The peptides can also be used to deliver cytotoxic agents to tumours with profound efficacy. Remarkably, the peptides demonstrate very fast tumour penetration and retention coupled with rapid clearance from systemic circulation.
Whilst the generation and delivery of peptide therapeutics represent significant challenges, the simple storage of peptides can be problematic. Hao Luo from Merck explained the problem of peptide fibrillation (the rapid aggregation of peptides in solution) and methods for mitigating the risks of fibrillation. It turns out that a super-fast high temperature and high pH treatment using flow chemistry can significantly delay the onset of fibrillation without any significant degradation of the peptide.
Finally, Professor Mark Howarth (University of Oxford) presented his ground-breaking research in the development of peptide “superglues” derived from domains of bacterial proteins that form isopeptide bonds. The glues find utilities in a number of fields from protein stabilization (using the glues to cyclize proteins) to the formation of polypeptide superstructures. A notable example, which is being developed in the spin-out SpyBiotech Ltd, is the use of the peptide superglues in the generation of “plug-and-play” vaccine production, in which any antigen can be attached to a virus-like particle scaffold to produce highly effective vaccines.
Thanks to all those who presented. I will be following all of the developments with interest…