Spiegelmers

B. Kuhnast, S. Klussmann, F. Hinnen, R. Boisgard, B. Rousseau, J.P. Furste, B. Tavitian, F. Dolle, Fluorine-18- and iodine-125 labelling of Spiegelmers, J. Label. Compds Radiopharm. 46 (2003) 1205-1219. 

H. Hess-Stumpp, S. Klussmann, In vivo properties of an anti-GnRH Spiegelmer An example of an oligonucleotide-based therapeutic substance class, Proc. Nat. Acad. Sci. USA 99 (2002) 8898-8902. 

The insufficient stability of RNA, mentioned above, limits the use of RNA aptamers. However, some established techniques yield nuclease-resistant aptamers. One alternative is called the Spiegelmer approach [29], another method involves incorporation of 2 -methoxy purine nucleotides [30]. 

Spiegelmers are a new class of substance for a wide field of applications, especially drug design. Their functional properties can be compared with the action of monoclonal antibodies. The production of spiegelmers is as simple as the synthesis of other oligonudeotides because standard chemical methods, for example common phosphoramidite chemistry, can be employed. 

Fig. 3.4.2. Schematic representation of spiegelmer technology. A library of 1015 different oligonucleotides is synthesized and incubated with the mirror-image (or enantiomeric) form of a naturally occurring target. After several cycles of selection and amplification the enriched library is cloned in an appropriate vector and sequenced. Individualized binding oligonucleotides are further...

Fig. 3.4.4. Reciprocal chiral specificity. (A) The selected d-RNA sequence (aptamer) binds to the unnatural synthetic L-adenosine but not to D-adenosine and the corresponding l-RNA sequence (spiegelmer) recognizes naturally occurring D-adenosine but not L-adenosine. (B) The non-cognate interactions are approx. 9000-fold weaker than the intended interactions. (C)...

Fig. 3.4.5. Biological stability of an aptamer (D-oligonucleotide) and a spiegelmer (L-oligonucleotide) in human serum. Both oligonucleotides were incubated in buffered human serum and after the times indicated samples were taken and analyzed on a...

Spiegelmer conjugated Low serum titers after 35 days Low serum titers after 63 days... 

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