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.

Regiospecific Anomerisation of Acylated Glycosyl Azides and Benzoylated Disaccharides by Using TiCl4

“…Glycosyl triazoles have been prepared from the corresponding azide and α‐glycosyl azides have also been used for the synthesis of α‐glycosyl amides 11b. 28, 29 The number of α‐glycosyl azides is limited in the literature and, until now, these have usually been prepared by nucleophilic substitution of the β‐glycosyl halide 30…”

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2011–2012

“…Synthesis of C-linked triazole-containing analogues and their ability to inhibit ice recrystallization (Capicciotti et al, 2011) Antifreeze glycoproteins (homodimeric) TOF Studies on the effect of the number of sugar moieties on the antifreeze activity (Ahn et al, 2012b) (Boutureira et al, 2011) Glycopeptide aryl thioesters TOF Fmoc-based chain elongation. O-to Sacyl shift.…”

Antifreeze Peptides and Glycopeptides, and Their Derivatives: Potential Uses in Biotechnology

“…In contrast to the first 2 approaches, some of the triazole-containing AFGP analogues showed moderate RI activity, which suggests that a hydrophobic component ( i.e. , the methylene spacer) close to the sugar residue, as well as the length of the side chain bearing the triazole linkage, plays key roles in the activity [94] (Figure 7C).…”