AFGPs

A unique family of O-linked glycoproteins permits fish to live in the icy seawater of the Arctic and Antarctic regions where water temperature may reach as low as — 1.9°C. Antifreeze glycoproteins (AFGPs) are found in the blood of nearly all Antarctic fish and at least five Arctic fish. These glycoproteins have the peptide structure... 

Figure 7.39. The diversity of antifreeze proteins and antifreeze glycoproteins in marine fishes. Shown are the structures of four types of AFPs (I-IV) and the AFGP found in Antarctic notothenioids and Arctic cod. AFPs I-IV are shown as ribbon structures. The tripeptide repeat (-ala-ala-thr-) and carbohydrate moiety (galactosyl-lV-acetylgalactosamine) of AFGPs illustrate the key element of AFGP structures in noto-thenioid and Arctic cod.

Despite the occurrence of AFGPs in Antarctic notothenioids at concentrations that... 

The ability to inhibit the growth of ice has potential medical, industrial and commercial applications. Unfortunately, many of these applications have not been fully realized. One reason for this is that the isolation and purification of AFGP is a laborious and costly process often resulting in mixtures, making characterization difficult (5). Additional reasons include the fact that the AFGP mechanism of action is not understood at the molecular level and the nature of the protein-ice interface remains in question (6). 

Both models assume irreversible adsorption of AFGP onto the ice surface. However, neither model can explain the fact that high levels of adsorption are not observed at low concentrations. Consequently, alternate mechanisms have been proposed (JO). 

So far, all AFGP analogs prepared in our laboratory have utilized the L-lysine-glycine-glycine tripeptide unit that is radically different in structure than the core repeating tripeptide unit found in native AFGP. The threonine residue in native AFGP was replaced with lysine for two reasons. Firstly, recent work has demonstrated that an alanine-lysine rich polypeptide possessed weak antifreeze protein-specific activity (26). 

Secondly, the C-linked galactosyl-lysine residue in our analogs serves as a structural analog for the L-arginine residue occasionally substituted for L-threonine in AFGP 7-8 (Figure 4). 

Typical solid phase synthesis protocols were employed to assemble the tripeptide building blocks into C-link AFGP glycopolymers. The method is illustrated in Scheme 3. 

---