title: Development and Optimization of Glaser-Hay Bioconjugations.
abstract: The prevalence of bioconjugates in the biomedical sciences necessitates the development of novel mechanisms to facilitate their preparation. Towards this end, the translation of the Glaser-Hay coupling to an aqueous environment is examined, and its potential as a bioorthogonal conjugation reaction is demonstrated. This optimized, novel, and aqueous Glaser-Hay reaction is applied towards the development of bioconjugates utilizing protein expressed with an alkynyl unnatural amino acid. Unnatural amino acid technology provides a degree of bioorthognality and specificity not feasible with other methods. Moreover, the scope of the reaction is demonstrated through protein-small molecule couplings, small-molecule-solid-support couplings, and protein-solid-support immobilizations.
authors.affiliation: Department of Chemistry, College of William & Mary, P.O. Box 8795, Williamsburg, VA 23187 (USA).
authors.forename: Jessica S
authors.initials: JS
authors.lastname: Lampkowski
authors.affiliation: Department of Chemistry, College of William & Mary, P.O. Box 8795, Williamsburg, VA 23187 (USA).
authors.forename: Jordan K
authors.initials: JK
authors.lastname: Villa
authors.affiliation: California Institute of Biomedical Research, 11119 N. Torrey Pines Rd, La Jolla, CA 92037 (USA).
authors.forename: Travis S
authors.initials: TS
authors.lastname: Young
authors.affiliation: Department of Chemistry, College of William & Mary, P.O. Box 8795, Williamsburg, VA 23187 (USA). dyoung01@wm.edu.
authors.forename: Douglas D
authors.initials: DD
authors.lastname: Young
mesh_terms: D000480:Alkynes / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry; D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry / Q000378:metabolism; D002384:Catalysis; D003300:Copper / Q000737:chemistry; D008301:Maleimides / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D014867:Water / Q000737:chemistry
chemical_list: C504424:Alexa Fluor 488 C5-maleimide; D000480:Alkynes; D000596:Amino Acids; D008301:Maleimides; D009942:Organometallic Compounds; D011506:Proteins; C450681:phenyllithium; D014867:Water; D003300:Copper; D000604:Amino Acyl-tRNA Synthetases
keywords: Glaser-Hay; alkynes; bioconjugation; solid supports; unnatural amino acids