Structural Basis for Recognition of Guanosine by a Synthetic Tricyclic Cytosine Analogue: Guanidinium G-Clamp
✍ Scribed by Christopher J. Wilds; Martin A. Maier; Muthiah Manoharan; Martin Egli
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- German
- Weight
- 275 KB
- Volume
- 86
- Category
- Article
- ISSN
- 0018-019X
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✦ Synopsis
Abstract
An oligonucleotide analogue containing a novel heterocyclic analogue, the guanidinium G‐clamp, was designed to allow formation of five H‐bonds to guanosine. The guanidinium group was introduced postsynthetically by treatment of the deprotected oligonucleotide containing a free amino group with a solution of 1__H__‐pyrazole‐1‐carboxamidine and purified by a combination of size‐exclusion chromatography and reversed‐phase HPLC. A single incorporation of this modification into an oligodeoxynucleotide sequence was found to increase duplex stability by 13° and 16° per modification to RNA and DNA, respectively. Crystals of a self‐complementary decamer sequence containing this modification were grown and diffracted to 1‐Å resolution. The structure was solved by molecular replacement and revealed that the modification forms additional H‐bonds to O(6) and N(7) of guanosine through the amino and imino N‐atoms, respectively. The origins of enhanced duplex stability are also attributed to increased stacking interactions mediated by the phenoxazine moiety of the G‐clamp and formation of H‐bond networks between the positively charged guanidinium group, H~2~O molecules, and negatively charged O‐atoms from phosphates on the adjacent strand.