Prolonging the Half-Life of Peptides Using an Engineered Albumin-Binding Peptide
Christian Heinis
Associate Professor, EPFL
We have engineered an albumin-binding tag that allows non-covalent tethering of peptides to the long-lived serum protein albumin, in order to prevent their rapid renal clearance (Zorzi, A., et al., Nature Communications, 2017). The tag is based on a fatty acid that binds with weak affinity to albumin (around 1 uM) and a peptide moiety that contributes to the binding affinity to reach a Kd of 39 nM for human albumin. Conjugation of the tag to (bi)cyclic peptide binders of disease targets prolonged their half-life in rats and rabbits from a minutes to several hours.
In my talk, I will briefly show how we have developed the chimeric fatty acid/peptide albumin binding ligand and I wills present examples of published and unpublished peptides to which we have applied the tag. I will discuss the effects of the tag on the peptides' proteolytic stability in blood plasma in vitro and the half-life in vivo. Finally, I will speculate on why some peptides loose much of their activity and others not at all when they are conjugated via tags to albumin.
The main goal of Christian Heinis’ research is the development of therapeutics based on cyclic peptides. Towards this end, his laboratory is developing methods for synthesizing and screening large combinatorial libraries of cyclic peptides.
Christian Heinis has studied biochemistry/chemistry at the ETH Zurich. After a PhD in the research group of Prof. Dr. Dario Neri at ETH, he did two post-docs, the first one with Prof. Dr. Kai Johnsson at the EPFL and the second one with Sir Gregory Winter at the LMB-MRC in Cambridge, UK. In 2008 he started as Assistant Professor at EPFL (supported with an SNSF professorship) and was promoted in 2015 to Associate Professor.
Christian is a co-founder of Bicycle Therapeutics (BCYC) and the co-director of the NCCR Chemical Biology.