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Energetically important C-H···F-C pseudohydrogen bonding in water: evidence and application to rational design of oligonucleotides with high binding affinity

Energetically important C-H···F-C pseudohydrogen bonding in water: evidence and application to rational design of oligonucleotides with high binding affinity
Energetically important C-H···F-C pseudohydrogen bonding in water: evidence and application to rational design of oligonucleotides with high binding affinity
It is controversial whether organic fluorine can form energetically important hydrogen bonds in aqueous environments. We previously showed by NMR and molecular modeling that the unexpectedly high binding affinity of 2?F-ANA is largely due to a C?H···F?C pseudohydrogen bond at pyrimidine?purine steps. Comparisons of the melting of duplexes with identical sequence composition but a rearranged sequence confirm that energetically important fluorine-mediated pseudohydrogen bonding is in operation in these sequences. The effect is of particular importance when the H-bond donor (purine H8) is activated by the presence of fluorine at its own 2?-position. These results provide a rational method to increase the binding affinity of antisense oligonucleotides by placement of 2?F-ANA modifications at pyrimidine?purine steps.
0002-7863
728-731
Anzahaee, Maryam Yahyaee
a706400a-e6de-4818-bf3b-50884c9d3097
Watts, Jonathan K.
c4de85ee-aaa3-4e7d-99b3-147a4de4f01c
Alla, Nageswara R.
b8ed97ab-37bb-4967-a6d4-5d9ff8a65f04
Nicholson, Allen W.
b5d8bc5e-cf05-4592-b262-db329ab3af45
Damha, Masad J.
31a9645e-2a72-4cc5-aa35-b82a16f1d535
Anzahaee, Maryam Yahyaee
a706400a-e6de-4818-bf3b-50884c9d3097
Watts, Jonathan K.
c4de85ee-aaa3-4e7d-99b3-147a4de4f01c
Alla, Nageswara R.
b8ed97ab-37bb-4967-a6d4-5d9ff8a65f04
Nicholson, Allen W.
b5d8bc5e-cf05-4592-b262-db329ab3af45
Damha, Masad J.
31a9645e-2a72-4cc5-aa35-b82a16f1d535

Anzahaee, Maryam Yahyaee, Watts, Jonathan K., Alla, Nageswara R., Nicholson, Allen W. and Damha, Masad J. (2011) Energetically important C-H···F-C pseudohydrogen bonding in water: evidence and application to rational design of oligonucleotides with high binding affinity. Journal of the American Chemical Society, 133 (4), 728-731. (PMID:21171597)

Record type: Article

Abstract

It is controversial whether organic fluorine can form energetically important hydrogen bonds in aqueous environments. We previously showed by NMR and molecular modeling that the unexpectedly high binding affinity of 2?F-ANA is largely due to a C?H···F?C pseudohydrogen bond at pyrimidine?purine steps. Comparisons of the melting of duplexes with identical sequence composition but a rearranged sequence confirm that energetically important fluorine-mediated pseudohydrogen bonding is in operation in these sequences. The effect is of particular importance when the H-bond donor (purine H8) is activated by the presence of fluorine at its own 2?-position. These results provide a rational method to increase the binding affinity of antisense oligonucleotides by placement of 2?F-ANA modifications at pyrimidine?purine steps.

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e-pub ahead of print date: 20 December 2010
Published date: 2 February 2011
Organisations: Chemistry

Identifiers

Local EPrints ID: 340222
URI: https://eprints.soton.ac.uk/id/eprint/340222
ISSN: 0002-7863
PURE UUID: 1f852160-b27e-4960-b18f-494bcfd62068

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Date deposited: 15 Jun 2012 12:37
Last modified: 25 Oct 2017 08:34

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