Synthesis and evaluation of linear CuAAC-oligomerized antifreeze neo-glycopeptides

Antifreeze glycoproteins (AFGPs) are important naturally occurring biological antifreezes that lower the freezing point of a solution, thereby preventing uncontrolled ice growth. These compounds also inhibit ice recrystallization. Described in this paper is a synthetic antifreeze glycopeptide-based polymer synthesized from an azide/alkyne glycopeptide building block by partial reduction of the azide and subsequent copper catalyzed azide alkyne cycloaddition (CuAAC) polymerization to obtain linear oligomers. To compare the activity with native AFGPs, a linear dodecapeptide (oligomer with four repeating units) was synthesized and isolated which had a comparable length to AFGP-8, the lowest molecular mass glycoprotein AFGP found in nature. In terms of ice recrystallization inhibition (IRI) activity, the triazole-based oligomers displayed only modest IRI activity compared with AFGP-8 and a previously described carbon-linked AFGP analogue. However, CD spectroscopy showed that the triazole-based tetramer possessed a similar secondary structure to the related amide based carbon-linked AFGP tetramer based on AFGP-8.