title: Exploring Tyrosine-Triazolinedione (TAD) Reactions for the Selective Conjugation and Cross-Linking of N-Carboxyanhydride (NCA) Derived Synthetic Copolypeptides.
abstract: Highly efficient functionalization and cross-linking of polypeptides is achieved via tyrosine-triazolinedione (TAD) conjugation chemistry. The feasibility of the reaction is demonstrated by the reaction of 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) with tyrosine containing block copolymer poly(ethylene glycol)-Tyr4as well as a statistical copolymer of tyrosine and lysine (poly(Lys40-st-Tyr10)) prepared form N-carboxyanhydride polymerization. Selective reaction of PTAD with the tyrosine units is obtained and verified by size exclusion chromatography and NMR spectroscopy. Moreover, two monofunctional and two difunctional TAD molecules are synthesized. It is found that their stability in the aqueous reaction media significantly varied. Under optimized reaction conditions selective functionalization and cross-linking, yielding polypeptide hydrogels, can be achieved. TAD-mediated conjugation can offer an interesting addition in the toolbox of selective (click-like) polypeptide conjugation methodologies as it does not require functional non-natural amino acids.
authors.affiliation: School of Chemical Sciences, Dublin City University, Glasnevin, Dublin, 9, Ireland.
authors.forename: Saltuk B
authors.initials: SB
authors.lastname: Hanay
authors.affiliation: DSM Ahead, Urmonderbaan 22, Geleen, 6167, RD, the Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: Ritzen
authors.affiliation: School of Chemistry, University College Dublin, Belfield, Dublin, 4, Ireland.
authors.forename: Dermot
authors.initials: D
authors.lastname: Brougham
authors.affiliation: DSM Ahead, Urmonderbaan 22, Geleen, 6167, RD, the Netherlands.
authors.forename: Aylvin A
authors.initials: AA
authors.lastname: Dias
authors.affiliation: Department of Pharmaceutical and Medicinal Chemistry, Royal College of Surgeons in Ireland, 123 St. Stephens Green, Dublin, 2, Ireland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Heise
mesh_terms: D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*; D014227:Triazines / Q000737:chemistry*; D014443:Tyrosine / Q000737:chemistry*
chemical_list: D010455:Peptides; D014227:Triazines; D014443:Tyrosine
keywords: N-carboxyanhydrides; click reactions; cross-linking; hydrogels; polypeptides