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Use of OPeC™ Reagents to Conjugate RNA

As the OPeC™ technology was developed specifically for DNA-peptide conjugations, little or no work to our knowledge has been done using it for RNA equivalents. We ourselves have not used it for that application. There was one paper on a native ligation approach that predated the OPeC™ method (McPherson et al, Synlett S1, 978, 1999) which describes an RNA with a 5'-S-thioester and a peptide N-terminal cysteine. This preliminary report only described one example and little or no purification.

Although, on paper, the OPeC™ method could be applied to RNA-peptide conjugations, the main issue will be whether the conditions of removal of the 2'-protecting groups during RNA synthesis are compatible with use of the S-t-butylthio-protection on the cysteine linker. Although we have not tried this, we suspect that the fluoride deprotection for removal of TBDMS or TOM could be a problem. It might be usable with Dharmacon chemistry, possibly, since the 2'-deprotection there uses acid.

In general very little work has appeared in the literature about RNA-peptide conjugates. The coupling of siRNA strands to peptides is of interest at the moment however we are not aware of any successful published results in this regard.

This whole area of RNA-peptide conjugates is very much in it's infancy compared to DNA. In essence, each experiment requires to be researched and evaluated under it's own merits. We are unable, for example, to suggest a "typical" protocol for the OPeC™ kit for RNA in the way we do for DNA.

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