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. Therefore, ice recrystallization inhibition (IRI) activity is a very desirable property for an effective cryoprotectant. Antifreeze proteins (AFPs) and antifreeze glycoproteins (AFGPs) were the first compounds discovered with this property, however they are poor cryoprotectants due to their unique ability to bind to ice and alter habits of ice crystals. Consequently, AFGP analogues with “custom-tailored” antifreeze activity have been developed which exhibit potent IRI activity but do not bind to ice. Subsequent to this, it was reported that simple mono- and disaccharides exhibit moderate IRI activity and this has ultimately facilitated the discovery of several small carbohydrate-based ice recrystallization inhibitors with IRI activity similar to that of native AFGP-8. This represents a major advancement in the field of ice recrystallization inhibitors (IRIs). The recent developments of IRIs will be reviewed, focusing on novel small molecules that have great potential for use as cryoprotectants.