The ability to precisely target a protein of interest has many applications in medicine, including for the targeted delivery of radiation. To design molecules with this ‘homing’ functionality, we often engineer peptide and protein scaffolds, a process which borrows concepts from evolutionary diversification whereby new molecules acquire new function but retain shape resemblance to its parent. However, in practice, there are several design and technical challenges, which relate to the complexity to navigating the structural diversity of the scaffolds and optimising the pharmacophore to be inherited in the designed analogues. In this talk, I will discuss different approaches we have investigated for scaffold engineering, including structure-guided and computational approaches to match peptide pharmacophores to a disulfide-rich peptide scaffold, highlighting an example in which we grafted hotspots onto a new-to-nature scaffold; recombinant library methods to optimise contacts with the target protein; and recent attempts to downscale drug design of disulfide-rich peptides in ‘picoreactors’. We hope to continue to advance these methods so that we can design drugs with the desired function more efficiently.

Biography

Dr Conan Wang is a Group Leader at the Institute for Molecular Bioscience (IMB) and holds an ARC Future Fellowship. He leads a team focused on the computational and molecular engineering of peptides. Dr Wang earned his PhD in the biophysical characterisation of circular peptides from UQ in 2009. He then completed postdoctoral studies with the support of an NHMRC Early Career Fellowship, researching structures and binding interactions of neuronal proteins at the Hong Kong University of Science and Technology, and host-pathogen proteins at the Griffith University Institute for Drug Discovery. Dr Wang returned to UQ about a decade ago and has since been heavily involved in drug design projects with agricultural and pharmaceutical industry partners. His research investigates computational and molecular methods to engineer peptides and proteins, enhancing their functions and pharmacokinetic properties. He has authored over 100 publications in peer-reviewed international journals, which have received about 6,000 citations, and is an inventor on three patents. His scientific achievements have been recognised with over 30 national and international awards, and he has presented at numerous national and international conferences.