title: Synthesis of C-linked triazole-containing AFGP analogues and their ability to inhibit ice recrystallization.
abstract: C-Linked antifreeze glycoprotein (C-AFGP) analogues have been shown to have potent ice recrystallization inhibition (IRI) activity. However, the lengthy synthesis of these compounds is not amenable to large-scale preparation for the many commercial, industrial, and medical applications that exist. This paper describes the synthesis of triazole-containing AFGPs using a convergent solid-phase synthesis (SPS) approach in which multiple carbohydrate derivatives are coupled to a resin-bound synthetic peptide in a single step. Modified "Click" conditions using dry DMF as solvent with catalytic Cu(II), sodium ascorbate, and microwave radiation afforded the synthesis of AFGP analogues 9-12 in 16-54% isolated yield. Compound 9 demonstrated no IRI activity, while compounds 10, 11, and 12 were moderate inhibitors of ice recrystallization. These results suggest that, while the triazole group is a structural mimetic of an amide bond, the amide bond in C-AFGP analogue 3 is an essential structural feature necessary for potent IRI activity.
authors: Department of Chemistry, D'Iorio Hall, 10 Marie Curie, University of Ottawa , Ottawa, Ontario, Canada, K1N 6N5.
authors: Chantelle J
authors: CJ
authors: Capicciotti
authors: John F
authors: JF
authors: Trant
authors: Mathieu
authors: M
authors: Leclère
authors: Robert N
authors: RN
authors: Ben
mesh_terms: D021301:Antifreeze Proteins / Q000737:chemistry*; D003460:Crystallization; D007053:Ice; D015394:Molecular Structure; D013237:Stereoisomerism; D014230:Triazoles / Q000737:chemistry*
chemical_list: D021301:Antifreeze Proteins; D007053:Ice; D014230:Triazoles