The next generation: The effect of ibuprofen conjugation to hydrophilic second-generation antisense oligonucleotides on the binding affinity for serum albumin has been evaluated. The conjugation (see structure) offers a chemical solution for improving the pharmacokinetic distribution of 2′-O-methoxyethyl phosphodiester (PO) derivatives (RNA analogues). These compounds could provide an alternative solution to the nonspecific toxic side effects displayed by first-generation 2′-deoxyphosphorothioate (PS) antisense oligonucleotides.
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Manoharan et al. (2002) studied this question.
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