title: Tunable thioesters as "reduction" responsive functionality for traceless reversible protein PEGylation.
abstract: Disulfide has been the only widely used functionality to serve as a reduction responsive trigger in drug delivery. We introduce thioester as a novel thiol responsive chemistry for drug delivery, whose reactivity can be conveniently modulated by choosing the appropriate steric environment around the thioester. Compared with disulfides, thioesters are facile to synthesize and have an order of magnitude broader kinetic tunability. A novel traceless reversible protein PEGylation reagent is developed based on thioester chemistry.
authors.affiliation: Department of Pharmacology, Dan L. Duncan Cancer Center, and Cardiovascular Research Institute, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Chen
authors.forename: Mingkun
authors.initials: M
authors.lastname: Zhao
authors.forename: Fude
authors.initials: F
authors.lastname: Feng
authors.forename: Antons
authors.initials: A
authors.lastname: Sizovs
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
mesh_terms: D004951:Esterification / Q000187:drug effects; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D008958:Models, Molecular; D010084:Oxidation-Reduction / Q000187:drug effects; D011092:Polyethylene Glycols / Q000737:chemistry*; D011487:Protein Conformation; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000737:chemistry* / Q000378:metabolism
chemical_list: D013438:Sulfhydryl Compounds; D053221:TNF-Related Apoptosis-Inducing Ligand; D011092:Polyethylene Glycols; D005978:Glutathione