title: Protein functionalization revised: N-tert-butoxycarbonylation as an elegant tool to circumvent protein crosslinking.
abstract: The protection of primary amines available in proteins holds great potential to introduce a plethora of diverse functionalities along the protein backbone (e.g., via its carboxylic acid or alcohol moieties) while circumventing the crosslinking issue using conventional approaches. This paper reports on a straightforward and efficient proof-of-concept including the chemoselective N-tert-butyloxycarbonylation of the primary amines in the protein gelatin (gel-NH-BOC), followed by introducing crosslinkable methacrylamide moieties. The reaction is performed successfully under relatively mild conditions (50 °C). Following selective protein functionalization, the deprotection is realized by adding a catalytic amount of an aqueous hydrogen chloride solution. The present communication illustrates the occurrence of a straightforward and selective deprotection procedure, which is typically required to circumvent the occurrence of acidic hydrolysis of the protein backbone. The results hold promise for a large range of biomedical applications in which the presence of primary amines is essential for preserving the biological activity.
authors.affiliation: Polymer Chemistry and Biomaterials Group, University Ghent, Krijgslaan 281, 9000, Gent, Belgium.
authors.forename: Ine
authors.initials: I
authors.lastname: Van Nieuwenhove
authors.forename: Birgit
authors.initials: B
authors.lastname: Stubbe
authors.forename: Geert-Jan
authors.initials: GJ
authors.lastname: Graulus
authors.forename: Sandra
authors.initials: S
authors.lastname: Van Vlierberghe
authors.forename: Peter
authors.initials: P
authors.lastname: Dubruel
mesh_terms: D000178:Acrylamides / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000737:chemistry*; D005780:Gelatin / Q000737:chemistry*; D006851:Hydrochloric Acid / Q000737:chemistry
chemical_list: D000178:Acrylamides; D000588:Amines; D003432:Cross-Linking Reagents; D005780:Gelatin; C045985:methacrylamide; D006851:Hydrochloric Acid
keywords: N-Boc protection; carbodiimide coupling; gelatin; modification