(No) twist in the tale for icefish protein

A cyclic peptide has shattered an established theory about fish antifreeze.

The antifreeze glycoprotein (AFGP) was discovered in the 1960s in the blood and body fluids of the Antarctic icefish. It allows the fish to survive at temperatures as low as -2 °C by binding to small ice crystals and preventing them from growing to a size where they would be fatal.

Antifreeze glycoprotein AFGP allows Antarctic icefish to survive the cold © Uwe Kils

Shin-Ichiro Nishimura of the Hokkaido University, Sapporo, Japan, designs synthetic analogues of natural AFGPs (syAFGPs) in an effort to understand the connection between their structure and their antifreeze properties. Earlier results from Nishimura's team have implied that the proteins need to contain a helix-type structure to possess antifreeze activity. However, the group has now made cyclic analogues (cyAFGPs) without the helix, which show a significant anti ice-growth effect. The researchers say the finding is the only exception to the established theory that relates the AFGPs' antifreeze activity to their helical structure.

The team made the new peptides using an efficient and facile method which gives only cyAFGPs without contamination of linear glycopeptide intermediates. Peter Davies, an expert in antifreeze proteins, from Queen's University in Kingston, Canada, says: 'This method should eliminate the helical structure of the linear AFGPs. And yet cyclic versions of these glycopeptides, some as small as two repeating tripeptide units, have antifreeze activity.'

"The researchers say the finding is the only exception to the established theory that relates the AFGPs' antifreeze activity to their helical structure"

Nishimura says that further conformational studies of the cyAFGPs will reveal the structural motif required for the peptides' affinity with the ice lattice, helping towards understanding how the compounds exert their antifreeze properties.

'The importance of the novel method for the synthesis of cyclic peptides should also be emphasised,' Nishimura adds, 'because cyclic peptides and cyclic modified-peptides are potent candidates of therapeutic reagents such as anti-virus infection.'

Sandra Fanjul

http://www.rsc.org/Publishing/Journals/cb/Volume/2009/3/icefish_protein.asp