Open AccessTuning protein half-life in mouse using sequence-defined biopolymers functionalized with lipids
Author(s) -
Koen Vanderschuren,
Pol ArranzGibert,
Minsoo Khang,
Hadar Dagan,
Alice Gaudin,
Fan Yang,
Ewa FoltaStogniew,
W. Mark Saltzman,
Miriam Amiram,
Farren J. Isaacs
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2103099119
Subject(s) - lipid anchored protein , bioorthogonal chemistry , fusion protein , protein engineering , peptide , computational biology , biochemistry , peptide sequence , immunogenicity , sequence (biology) , chemistry , biology , combinatorial chemistry , recombinant dna , genetics , gene , antibody , apoptosis , autophagy , click chemistry , enzyme
Significance Functionalization of proteins and biopolymers with chemical modifications can be utilized to alter their chemical and biophysical properties. In contrast to traditional chemical functionalization strategies, the use of nonstandard amino acids enables precise positioning of functional groups. Here, we report that multisite conjugation of fatty acids, at precise sites harboring genetically encoded nonstandard amino acids with bioorthogonal chemical handles, can be employed to tune the half-life of proteins in a mouse model. This programmable approach could offer a technical foundation for the modification of protein and peptide therapeutics to improve their efficacy or pharmacokinetic profile (e.g., to prevent rapid clearance and reduce frequency of administration).