Protein and DNA destabilization by osmolytes: The other side of the coin

Singh, Laishram Rajendrakumar; Poddar, Nitesh Kumar; Dar, Tanveer Ali; Kumar, Raj; Ahmad, Faizan

doi:10.1016/j.lfs.2010.10.020

Cited by 97 publications

(85 citation statements)

References 121 publications

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“…Destabilization by osmolytes has recently been 147 documented under a variety of conditions (Singh et al, 2011), and destabilization at low 148 concentrations followed by stabilization at higher concentrations has been seen with polyols and 149 glucose (Romero et al, 2009). The fact that this trend has not been observed before with amino 150 acids could simply be an artefact of the scarcity of data for protein stability in presence of osmolytes 151 at concentrations below 100 mM.…”

Section: Glycine 100mentioning

confidence: 99%

Controlling protein stability: Mechanisms revealed using formulations of arginine, glycine and guanidinium HCl with three globular proteins

Platts

Falconer

2015

International Journal of Pharmaceutics

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Section: Glycine 100mentioning

confidence: 99%

Controlling protein stability: Mechanisms revealed using formulations of arginine, glycine and guanidinium HCl with three globular proteins

Platts

Falconer

2015

International Journal of Pharmaceutics

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“…17,18 Evidence from several groups indicates that the use of multiple cryoprotectants from the different families above, such as trehalose and proline, 16 or trehalose and glycerol, 19 exhibit improved cellular survival compared with either cryopreservative alone, suggesting that additive 13 or synergistic stabilizing effects are possible when multiple cryopreservatives are used. 20 However, the concentrations of these cryoprotectants dictate whether they will be stabilizing or destabilizing 21,22 and concentrations that result in stabilization optimums may differ when cryoprotectants are combined. 23 In a previous study, we established our ability to optimize the composition of a multicomponent osmolyte solution 7 using a computational algorithm.…”

Section: Introductionmentioning

confidence: 99%

Combinations of Osmolytes, Including Monosaccharides, Disaccharides, and Sugar Alcohols Act in Concert During Cryopreservation to Improve Mesenchymal Stromal Cell Survival

Pollock

Moller-Trane

et al. 2016

Tissue Engineering Part C: Methods

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There is demand for non-dimethyl sulfoxide (DMSO) cryoprotective agents that maintain cell viability without causing poor postthaw function or systemic toxicity. The focus of this investigation involves expanding our understanding of multicomponent osmolyte solutions and their ability to preserve cell viability during freezing. Controlled cooling rate freezing, Raman microscopy, and differential scanning calorimetry (DSC) were utilized to evaluate the differences in recovery and ice crystal formation behavior for solutions containing multiple cryoprotectants, including sugars, sugar alcohols, and small molecule additives. Postthaw recovery of mesenchymal stem cells (MSCs) in solutions containing multiple osmolytes have been shown to be comparable or better than that of MSCs frozen in 10% DMSO at 1°C/min when the solution composition is optimized. Maximum postthaw recovery was observed in these multiple osmolyte solutions with incubation times of up to 2 h before freezing. Raman images demonstrate large ice crystal formation in cryopreserved cells incubated for shorter periods of time (*30 min), suggesting that longer permeation times are needed for these solutions. Recovery was dependent upon the concentration of each component in solution, and was not strongly correlated with osmolarity. It is noteworthy that the postthaw recovery varied significantly with the composition of solutions containing the same three components and this variation exhibited an inverted U-shape behavior, indicating that there may be a ''sweet spot'' for different combinations of osmolytes. Raman images of freezing behavior in different solution compositions were consistent with the observed postthaw recovery. Phase change behavior (solidification patterns and glass-forming tendency) did not differ for solutions with similar osmolarity, but differences in postthaw recovery suggest that biological, not physical, methods of protection are at play. Lastly, molecular substitution of glucose (a monosaccharide) for sucrose (a disaccharide) resulted in a significant drop in recovery. Taken together, the information from these studies increases our understanding of non-DMSO multicomponent cryoprotective solutions and the manner by which they enhance postthaw recovery.

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“…The destabilization of DNA by osmolytes has also been observed [79] and role in modulating protein-DNA interactions has been discussed [80]. For example, mitigation of the binding of ERG1 to DNA in a differential manner has been reported.…”

Section: Osmolytes and Dnamentioning

confidence: 99%

Biological Wonders of Osmolytes: The Need to Know More

Judy¹,

Kishore²

2016

Biochem Anal Biochem

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Nature has selected osmolytes to protect intracellular macromolecules against denaturing stress conditions. These molecules are accumulated in the intracellular environment at considerably high concentrations. In general, osmolytes are known to stabilize proteins. However, under certain conditions, their destabilizing properties have also been pointed out. A careful qualitative and quantitative understanding of the mechanism of action of osmolytes with proteins from native to different stages of aggregation/fibrillation is extremely important in rational drug design. This review highlights the importance of naturally occurring osmolytes in protein folding, stabilization, and prevention of fibrillation/aggregation related diseases among others. Continued efforts are required to get quantitative insights into osmolyte-protein interactions along with experimental evidences for the much claimed preferential exclusion/preferential hydration phenomenon of osmolyte action. Mechanistic insights into the disease associated roles of osmolytes needs special attention.

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Protein and DNA destabilization by osmolytes: The other side of the coin

Cited by 97 publications

References 121 publications

Controlling protein stability: Mechanisms revealed using formulations of arginine, glycine and guanidinium HCl with three globular proteins

Controlling protein stability: Mechanisms revealed using formulations of arginine, glycine and guanidinium HCl with three globular proteins

Combinations of Osmolytes, Including Monosaccharides, Disaccharides, and Sugar Alcohols Act in Concert During Cryopreservation to Improve Mesenchymal Stromal Cell Survival

Biological Wonders of Osmolytes: The Need to Know More

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