Plant Derived Cholesterol Modifications - A Comparison of Commercially Available Cholesterol Phosphoramidites and Solid Supports for use in Oligonucleotide Synthesis of DNA and RNA (TC and TBDMS chemistries)

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Poster presented at TIDES 2010 in Boston.

Abstract

The use of cholesterol labelled oligonucleotides as a means of improving cell penetration is well known and with increasing frequency these are
entering into various stages of clinical trials. As regulatory guidelines become more stringent, there is a need to have non-animal derived cholesterol building blocks. Link Technologies Ltd. has developed the latter in the form of 5’-cholesterol cyanoethyl phosphoramidites and a 3’-cholesterol solid support where the cholesterol is derived from plants. A comparison of commercially available cholesterol phosphoramidites and solid supports for use in oligonucleotide synthesis of DNA and RNA (TBDMS and TC chemistry) using varying deprotection conditions was carried out. Oligonucleotides modified with dR cholesterol were also included.

In particular, degradation during deprotection was investigated where the cholesterol modification can potentially be lost via cleavage at the carbamate
bond, the anomeric positon or elimination of the entire modification during base deprotection as a result of the 1,2-diol arrangement where the terminal OH reacts with the neighbouring phosphate bond. The optimum deprotection conditions for each of these modifications were then determined.

Related products: 2170, 2189, 2394.

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