<i>O</i>-Aryl-Glycoside Ice Recrystallization Inhibitors as Novel Cryoprotectants: A Structure–Function Study

Capicciotti, Chantelle J.; Mancini, Ross S.; Turner, Tracey R.; Koyama, Toshie; Alteen, Matthew G.; Doshi, Malay; Inada, Takaaki; Acker, Jason P.; Ben, Robert N.

doi:10.1021/acsomega.6b00163

Cited by 38 publications

(47 citation statements)

References 51 publications

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“…Additional work showed that supplementing glycerol with milimolar concentrations of O ‐aryl‐ d ‐glycosides 41 , 42 , 43 , 45 , and 47 resulted in increased post‐thaw cell viabilities by 30%–50% and 70%–80% intact RBCs post‐thaw. This demonstrates that cryopreservation is still successful with 15% glycerol (Figure ), which also greatly reduces post‐thaw deglycerolization times . In addition, these IRIs were very effective at protecting RBCs against transient warming effects .…”

Section: Modern Cryobiology and The Use Of “Antifreezes” As Cryoprotementioning

confidence: 83%

“…Para ‐methoxyphenyl‐β‐ d ‐glycosides (PMP) were the first in their class to be tested as inhibitors for ice recrystallization, and unlike previous observations, the glucose derivative β‐PMP‐Glc ( 41 ) was significantly more active than its galactose ( 39 ) and mannose ( 40 ) derivative . Several para‐substituted derivatives of d ‐glucose, d ‐galactose, and d ‐mannose were also evaluated for IRI activity . The results suggested that electronic effects do not influence the IRI activity of O ‐aryl‐glycosides in any predictable fashion as strongly electron withdrawing substituents (–F, –Br, –Cl, –CF 3 ) resulted in moderate to high activity, but para‐substitution with –NO 2 resulted in minimal IRI activity.…”

Section: Inhibiting Ice Recrystallization Using Small Moleculesmentioning

confidence: 96%

“…The results suggested that electronic effects do not influence the IRI activity of O ‐aryl‐glycosides in any predictable fashion as strongly electron withdrawing substituents (–F, –Br, –Cl, –CF 3 ) resulted in moderate to high activity, but para‐substitution with –NO 2 resulted in minimal IRI activity. However, changing to an α‐linkage or converting the anomeric oxygen of β‐PMP‐Glc to nitrogen or sulfur resulted in a significant decrease in IRI activity . In the N ‐aryl‐ d ‐aldonamide series, several substituted benzyl and phenyl analogs were synthesized and evaluated for their IRI activity.…”

Section: Inhibiting Ice Recrystallization Using Small Moleculesmentioning

confidence: 99%

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Designing the next generation of cryoprotectants – From proteins to small molecules

et al. 2018

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During the past decade, there have been many exciting advances in the fields of cellular therapies, regenerative medicine, and tissue engineering. However, current cryopreservation strategies and protocols result in inferior product after thawing. Thus, novel cryoprotectants and protocols capable of meeting the high‐quality product(s) necessary for these therapies are urgently required. The search for new and improved cryoprotectants has been ongoing but novel small molecule ice recrystallization inhibitors, originally developed from naturally occurring antifreeze proteins, have demonstrated tremendous promise and will play a significant role in fully translating cellular and regenerative therapies into the clinical environment.

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Section: Modern Cryobiology and The Use Of “Antifreezes” As Cryoprotementioning

confidence: 83%

Section: Inhibiting Ice Recrystallization Using Small Moleculesmentioning

confidence: 96%

Section: Inhibiting Ice Recrystallization Using Small Moleculesmentioning

confidence: 99%

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Designing the next generation of cryoprotectants – From proteins to small molecules

et al. 2018

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“…11,[14][15][16][17][18] The Ben laboratory has been designing and synthesizing small molecule IRIs and has demonstrated their advantages in many in vitro cellular systems. 4,[19][20][21][22][23] The structure of aldonamide-derived IRI is shown in Fig. 1.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of ice recrystallization during cryopreservation of cord blood grafts improves platelet engraftment

et al. 2020

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BACKGROUND Platelet engraftment following cord blood (CB) transplantation remains a significant hurdle to this day. The uncontrolled growth of ice, a process referred to as ice recrystallization, is one of several mechanisms that lead to cell loss and decreased potency during freezing and thawing. We hypothesized that reducing cell damage induced by ice recrystallization in CB units (CBUs) would reduce losses of stem and progenitor cells and therefore improve engraftment. We previously demonstrated that the ice recrystallization inhibitor (IRI) N‐(2‐fluorophenyl)‐D‐gluconamide (IRI 2) increases the postthaw recovery of CB progenitors. Herein, we set out to ascertain whether IRI 2 can enhance platelet and bone marrow engraftment activity of hematopoietic stem cells (HSCs) in cryopreserved CBUs using a serial transplantation model. STUDY DESIGN AND METHODS CBUs were processed following standard volume/red blood cell reduction procedure and portions frozen with dimethyl sulfoxide (DMSO) supplemented or not with IRI 2. Thawed CB samples were serially transplanted into immunodeficient mice. RESULTS Our results show that supplementation of DMSO with IRI 2 had several beneficial effects. Specifically, higher levels of human platelets were observed in the peripheral blood (p < 0.05; n = 4) upon transplant of CBUs preserved with the IRIs. In addition, human BM chimerism and the number of human CFU progenitors in the bone marrow were superior in IRI 2 recipients compared to DMSO recipients. Moreover, IRI 2 had no negative impact on the multilineage differentiation and self‐renewal activities of HSCs. DISCUSSION Taken together, these results demonstrate that supplementation of a hematopoietic graft with IRI can improve the postthaw engraftment activities of HSCs.

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“…Carbohydrates alone have some weak IRI, with the hypothesis that their degree of hydration correlates with activity, but whether this relationship holds when attached to the AFGP backbone remains unknown 44 , 49 . Ben and co-workers were the first to report the synthesis of low molecular weight carbohydrate derived small molecules possessing IRI activity 46 , 49 , 50 . Inspired by the obvious presentation of hydrophobic faces in AF(G)Ps, (Fig.…”

Section: Small Molecule and Peptide Based Mimicsmentioning

confidence: 99%

Polymer mimics of biomacromolecular antifreezes

et al. 2017

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Antifreeze proteins from polar fish species are remarkable biomacromolecules which prevent the growth of ice crystals. Ice crystal growth is a major problem in cell/tissue cryopreservation for transplantation, transfusion and basic biomedical research, as well as technological applications such as icing of aircraft wings. This review will introduce the rapidly emerging field of synthetic macromolecular (polymer) mimics of antifreeze proteins. Particular focus is placed on designing polymers which have no structural similarities to antifreeze proteins but reproduce the same macroscopic properties, potentially by different molecular-level mechanisms. The application of these polymers to the cryopreservation of donor cells is also introduced. Water is fundamental to all life on our planet, and despite it having a freezing point of 0˚C, Nature has evolved a series of unique adaptations to enable life to flourish in sub-zero climates, at high altitudes and at the Earth's poles. Such extremophiles include the wood frog (Lithobates sylvaticus) which can freeze solid over winter, tardigrades which can be desiccated and rehydrated and cold tolerant plants 1, 2 . The mechanisms of these cryoprotectants are varied, from enabling freeze-tolerance (being able to be frozen and then thawed) to freeze avoidance (preventing ice forming) and even freeze promotion (as a predatory mechanism) 3-6 .One particular adaptation is the production of macromolecular antifreezes (proteins and polysaccharides) which modulate ice formation and growth, and are found in freeze avoidant organisms. These can be broadly split into the antifreeze proteins (AFPs) and antifreeze glycoproteins (AFGPs). AFGPs are highly conserved, with a relatively simple repeat tripeptide structure and a disaccharide on every third amino acid, but are produced in a range of chain lengths. Conversely, AFPs are far more diverse, with several subdivisions, and can assume different structures; from beta barrels to alpha helices and vary in size (Fig. 1). They all have a few core properties (discussed in detail below) including the ability to inhibit ice recrystallization, shape ice crystals into unusual morphologies and to depress the freezing point in a noncolligative manner. The relative magnitude of each effect varies between individual AF(G)Ps and the exact mechanisms, involving ice-face recognition, are still under investigation. What is clear, is that the ability to tune and modify ice growth and formation has the potential for huge industrial and societal impact. For example, ice adhesion limits the performance of wind farms by up to 50% 7 , is a major problem for aircraft 8 and even impacts our understanding of how biological components affect our climate 9, 10 .Some AFPs have already found application in improving the texture of ice cream products by preventing ice crystal growth, and other food uses are under investigation 4,11 . A key potential field where AF(G)Ps could be applied is in cell and tissue cryopreservation where ice

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O-Aryl-Glycoside Ice Recrystallization Inhibitors as Novel Cryoprotectants: A Structure–Function Study

Cited by 38 publications

References 51 publications

Designing the next generation of cryoprotectants – From proteins to small molecules

Designing the next generation of cryoprotectants – From proteins to small molecules

Inhibition of ice recrystallization during cryopreservation of cord blood grafts improves platelet engraftment

Polymer mimics of biomacromolecular antifreezes

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