Book of Abstracts: Albany 2009

category image Albany 2009
Conversation 16
June 16-20 2009
© Adenine Press (2008)

Carbocyclic Sugars Constrained to North and South Conformations Stabilize and Control RNA Conformations

Carbocyclic sugars, which are constrained to north/south (C2'/C3' exo) conformations have A/B form that can alter the helical properties of RNA duplexes and rigidify nucleotides due to their locked sugar puckers. Two RNA structures, a RNA dodecamer and an HIV kissing loop complex where several nucleotides are replaced with north and south constrained sugars, are studied by Molecular dynamics (MD) simulations. The overall helical properties of a modified RNA dodecamer where nucleotides are replaced by north constrained sugars did not show any critical deviation from canonical A-form helix. However, a modified RNA dodecamer where nucleotides are replaced with south carbocyclic sugars shows a mixture of A- and B-form helical properties. In addition, this modified dodecamer shows total length extension due to the south constrained sugars. In the HIV kissing loop complex, north and south constrained sugars are substituted into flanking bases that an x-ray structure of the kissing loop complex showed contained C2' endo south sugar conformations. The overall RMSD of the modified HIV kissing loop complex was decreased compared to that of the normal kissing loop complex. The reduced RMSD in the modified kissing loop complex depends on both type of substituted constrained sugar conformations and substituted locations. The overall RMSD decrease is also obtained by substituting north constrained sugars into both kissing loop complex stems. In addition, it is found that the axial twisting along the HIV kissing loop complex can be controlled by substituting constrained sugars. These results suggest that the proper use of specific north or south carbocyclic sugars at specified locations in an RNA structure can stabilize and deform RNA structures to obtain defined RNA conformations with specific chemical properties and shapes for RNA nano-design.

Taejin Kim1
Victor E. Marquez2
Bruce A. Shapiro1

1Center for Cancer Research Nanobiology Program (CCRNP)
National Cancer Institute at Frederick
Frederick, MD 21702
2Laboratory of Medicinal Chemistry
National Cancer Institute at Frederick
Frederick, MD 21702

Phone: 301-846-5536
Fax: 301-846-5598
Email: bshapiro@ncifcrf.gov