R.D.G. is grateful to NSERC (CGS D) for a postgraduate scholarship. We thank Benoît Deschênes-Simard for X-ray crystallographic analyses.
Structure-Based Design of a Highly Constrained Nucleic Acid Analogue: Improved Duplex Stabilization by Restricting Sugar Pucker and Torsion Angle γ†
Article first published online: 22 AUG 2012
Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Angewandte Chemie International Edition
Volume 51, Issue 45, pages 11242–11245, November 5, 2012
How to Cite
Hanessian, S., Schroeder, B. R., Giacometti, R. D., Merner, B. L., Østergaard, M., Swayze, E. E. and Seth, P. P. (2012), Structure-Based Design of a Highly Constrained Nucleic Acid Analogue: Improved Duplex Stabilization by Restricting Sugar Pucker and Torsion Angle γ . Angew. Chem. Int. Ed., 51: 11242–11245. doi: 10.1002/anie.201203680
- Issue published online: 30 OCT 2012
- Article first published online: 22 AUG 2012
- Manuscript Revised: 6 JUL 2012
- Manuscript Received: 11 MAY 2012
- antisense agents;
- conformational restriction;
- structure-based design
Dual conformational restriction: A new, highly constrained modification of the α-L-locked nucleic acid (α-L-LNA) scaffold that locks the sugar furanose ring in an N-type configuration and also restricts rotation around torsion angle γ was synthesized (see scheme). This new modification increases the thermostability of an oligonucleotide duplex compared to using a single mode of constraint alone.