title: Polar Hinges as Functionalized Conformational Constraints in (Bi)cyclic Peptides.
abstract: Two polar hinges for cyclization of peptides have been developed, leading to bicyclic peptides and cyclized peptides with improved solubility and biological activity. Increasingly, we note that a good aqueous solubility of peptides is an absolute prerequisite, not only to allow handling and purification of our target peptides but also being crucial for biological activity characteristics. Compared to earlier hinges, the 1,1',1"-(1,3,5-triazinane-1,3,5-triyl)tris(2-bromoethanone) (TATB) and 2,4,6-tris(bromomethyl)-s-triazine (TBMT), each containing three nitrogen atoms are structurally similar but chemically very different. Both were accessible in a one-step fashion from bromoacetonitrile. TATB and TBMT are very suitable for the preparation of more soluble bicyclic peptides. Azide-modified TATB and TBMT derivatives provide hinges for the preparation of cyclized peptides for incorporation on scaffolds to afford protein mimics.
authors.affiliation: School of Chemistry, University of Glasgow, Joseph Black Building, University Avenue, Glasgow, G12 8QQ, UK.
authors.forename: Helmus
authors.initials: H
authors.lastname: van de Langemheen
authors.affiliation: School of Chemistry, University of Glasgow, Joseph Black Building, University Avenue, Glasgow, G12 8QQ, UK.
authors.forename: Valerijs
authors.initials: V
authors.lastname: Korotkovs
authors.affiliation: School of Chemistry, University of Glasgow, Joseph Black Building, University Avenue, Glasgow, G12 8QQ, UK.
authors.forename: Joachim
authors.initials: J
authors.lastname: Bijl
authors.affiliation: School of Chemistry, University of Glasgow, Joseph Black Building, University Avenue, Glasgow, G12 8QQ, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Wilson
authors.affiliation: Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, 1015, Lausanne, Switzerland.
authors.forename: Sangram S
authors.initials: SS
authors.lastname: Kale
authors.affiliation: Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, 1015, Lausanne, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Heinis
authors.affiliation: School of Chemistry, University of Glasgow, Joseph Black Building, University Avenue, Glasgow, G12 8QQ, UK.
authors.forename: Rob M J
authors.identifier: 0000-0001-8897-8975
authors.initials: RM
authors.lastname: Liskamp
mesh_terms: D032701:Biomimetics; D008968:Molecular Conformation; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D010456:Peptides, Cyclic
keywords: peptides; peptidomimetics; protein design; protein models; protein-protein interactions