Synthesis of a C-linked antifreeze glycoprotein building block containing an internal olefin

Abstract

Antifreeze glycoproteins (AFGPs) are polypeptide compounds found in the blood of Antarctic notothenioids and northern cod. These substances inhibit the growth and proliferation of ice in fish inhabiting sub-zero conditions. The structure of AFGPs, and the mechanism of ice growth inhibition at the molecular level have been a source of intense debate. Work in our laboratory involves the synthesis of AFGP analogues in an effort to discern the mechanism of ice growth inhibition and enhance antifreeze attributes for potential therapeutic applications. We have previously synthesized C-linked AFGP analogues possessing antifreeze properties (TH, RI and DIS). One such analogue, [OGG] 4[Gal], has exhibited recrystallization inhibition (RI) activity comparable to native AFGPs. An important structural feature of [OGG]4[Gal] is the presence of an amide bond. We report herein the synthesis of a C-linked AFGP building block with an internal olefin as an amide isostere, in an effort to elucidate the function of the amide bond in the recrystallization inhibition activity of [OGG]4[Gal].