Tuning protein half-life in mouse using sequence-defined biopolymers functionalized with lipids
Koen Vanderschuren, Pol Arranz‐Gibert, Minsoo Khang, Hadar Dagan, Alice Gaudin, Fan Yang, Ewa Folta‐Stogniew, W. Mark Saltzman, Miriam Amiram, Farren J. Isaacs
Abstract
-azidophenylalanine (pAzF). Precise lipidation of these pAzF residues generated a set of sequence-defined synthetic biopolymers with programmable binding affinity to albumin without ablating the activity of model fusion proteins, and with tunable blood serum half-lives spanning 5 to 94% of albumin's half-life in a mouse model. Our findings present a proof of concept for the use of genetically encoded bioorthogonal conjugation sites for multisite lipidation to tune protein stability in mouse serum. This work establishes a programmable approach to extend and tune the half-life of protein or peptide therapeutics and a technical foundation to produce functionalized biopolymers endowed with programmable chemical and biophysical properties with broad applications in medicine, materials science, and biotechnology.