Designing ice recrystallization inhibitors: from antifreeze (glyco)proteins to small molecules

Abstract

Ice recrystallization occurs during cryopreservation and is correlated with reduced cell viability after thawing.

Mimicking the Ice Recrystallization Activity of Biological Antifreezes. When is a New Polymer “Active”?

“…However, for the facially amphipathic molecules, with no evidence for ice binding, an alternative molecular level mechanism which can give rise to IRI is required. One proposal is that these can sit at the semi‐ordered water layer (sometimes referred to as quasi‐liquid layer, QLL, which is strictly a definition at surfaces)/bulk water interface, rather than directly interact with ice faces . If the compounds can disorder this region, they will not fit well with bulk water, nor semi‐ordered water later and hence the barrier to adding more water to the ice crystal is higher and slows recrystallization …”

“…C) Interruption of the bulk water/semi‐ordered water interface. Reproduced with permission . Copyright 2014, Royal Society of Chemistry.…”

“…The same group has reported a series of modified glycopeptides with potent IRI, with the distance between backbone [50] and glycan being important as well as backbone hydrophobicity. [51,52] Figure 4A shows anchored clathrate water on the surface of an AFP, which directs the binding to multiple ice planes (basal and prism) due to crystallographic matches. [53] Figure 4B shows a simulation of spruce budworm AFP and its hypothesized binding to the prism plane via coordinated water molecules providing a match.…”

Modulation of antifreeze activity and the effect upon post-thaw HepG2 cell viability after cryopreservation

“…This is due in part to non-specific toxic effects and the change in ice crystal habit caused by the irreversible binding of the AF(G)P to ice [10,12,67,79]. Thus, the rational design of ice recrystallization inhibitors lacking TH activity (and the ability to bind to ice) is a worthwhile goal [4,8,[30][31][32]63].…”

Small molecule ice recrystallization inhibitors enable freezing of human red blood cells with reduced glycerol concentrations

“…As a consequence, there has been tremendous interest in designing compounds that can inhibit ice recrystallization for cryopreservation [16][17][18][19][20][21] . Our laboratory has recently reported the rational design and synthesis of large Clinked glycoconjugates [22][23][24] as well as small molecules [25][26][27] that inhibit the process of ice recrystallization.…”