title: Strain-promoted azide-alkyne cycloaddition for protein-protein coupling in the formation of a bis-hemoglobin as a copper-free oxygen carrier.
abstract: Conventional chemical approaches to protein-protein coupling present challenges due to the intrinsic competition between the desired interactions of reagents with groups of the protein as well as reactions with water. Biorthogonal Cu(i)-catalyzed azide-alkyne cycloaddition (CuAAC)-processes provide a basis to direct reactivity without functional group interference. However, the requirement for Cu(i) in CuAAC leads to complications that result from the metal ion's interactions with the protein. In principle, a similar but metal-free alternative approach to coupling could employ the reaction of an alkyne that is strained in combination with an azide (strain-promoted azide-alkyne cycloaddition, SPAAC). The method is exemplified by the combination of a cyclooctyne derivative of hemoglobin with an azide-modified hemoglobin. The bis-hemoglobin tetramer that is produced has properties consistent with those sought for use as a hemoglobin-based oxygen carrier (HBOC).
authors.affiliation: Davenport Chemical Laboratories, Department of Chemistry, University of Toronto, Toronto, Ontario, Canada M5S 3H6. r.kluger@utoronto.ca.
authors.forename: Serena
authors.initials: S
authors.lastname: Singh
authors.affiliation: Davenport Chemical Laboratories, Department of Chemistry, University of Toronto, Toronto, Ontario, Canada M5S 3H6. r.kluger@utoronto.ca.
authors.forename: Ina S
authors.initials: IS
authors.lastname: Dubinsky-Davidchik
authors.affiliation: Davenport Chemical Laboratories, Department of Chemistry, University of Toronto, Toronto, Ontario, Canada M5S 3H6. r.kluger@utoronto.ca.
authors.forename: Ronald
authors.initials: R
authors.lastname: Kluger
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D001386:Azides / Q000737:chemistry*; D061565:Cycloaddition Reaction; D006454:Hemoglobins / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D010100:Oxygen / Q000378:metabolism*
chemical_list: D000480:Alkynes; D001386:Azides; D006454:Hemoglobins; D010100:Oxygen