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This was explained by unequal populations of the two diastereomers in the crystal structure of the complex of CUTr1 and the phosphorothioate-modified DNA. The preferred diastereomer formed more hydrogen bonds with the oxygen atoms and/or more hydrophobic contacts with the sulfur atoms than the other, revealing the origins of the enhanced affinity. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.Repression of cellular reprogramming in germ cells is critical to maintaining cell fate and fertilit