QSAR Accelerated Discovery of Potent Ice Recrystallization Inhibitors
10.1038/srep26403
Crossref journal-article
Springer Science and Business Media LLC
Scientific Reports (297)
Abstract

AbstractIce recrystallization is the main contributor to cell damage and death during the cryopreservation of cells and tissues. Over the past five years, many small carbohydrate-based molecules were identified as ice recrystallization inhibitors and several were shown to reduce cryoinjury during the cryopreservation of red blood cells (RBCs) and hematopoietic stems cells (HSCs). Unfortunately, clear structure-activity relationships have not been identified impeding the rational design of future compounds possessing ice recrystallization inhibition (IRI) activity. A set of 124 previously synthesized compounds with known IRI activities were used to calibrate 3D-QSAR classification models using GRid INdependent Descriptors (GRIND) derived from DFT level quantum mechanical calculations. Partial least squares (PLS) model was calibrated with 70% of the data set which successfully identified 80% of the IRI active compounds with a precision of 0.8. This model exhibited good performance in screening the remaining 30% of the data set with 70% of active additives successfully recovered with a precision of ~0.7 and specificity of 0.8. The model was further applied to screen a new library of aryl-alditol molecules which were then experimentally synthesized and tested with a success rate of 82%. Presented is the first computer-aided high-throughput experimental screening for novel IRI active compounds.

Bibliography

Briard, J. G., Fernandez, M., De Luna, P., Woo, Tom. K., & Ben, R. N. (2016). QSAR Accelerated Discovery of Potent Ice Recrystallization Inhibitors. Scientific Reports, 6(1).

Authors 5
  1. Jennie G. Briard (first)
  2. Michael Fernandez (additional)
  3. Phil De Luna (additional)
  4. Tom. K. Woo (additional)
  5. Robert N. Ben (additional)
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Dates
Type When
Created 9 years, 3 months ago (May 24, 2016, 1:17 p.m.)
Deposited 2 years, 7 months ago (Jan. 4, 2023, 9:39 a.m.)
Indexed 11 months, 2 weeks ago (Sept. 15, 2024, 9:16 a.m.)
Issued 9 years, 3 months ago (May 24, 2016)
Published 9 years, 3 months ago (May 24, 2016)
Published Online 9 years, 3 months ago (May 24, 2016)
Funders 0

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@article{Briard_2016, title={QSAR Accelerated Discovery of Potent Ice Recrystallization Inhibitors}, volume={6}, ISSN={2045-2322}, url={http://dx.doi.org/10.1038/srep26403}, DOI={10.1038/srep26403}, number={1}, journal={Scientific Reports}, publisher={Springer Science and Business Media LLC}, author={Briard, Jennie G. and Fernandez, Michael and De Luna, Phil and Woo, Tom. K. and Ben, Robert N.}, year={2016}, month=may }