Skip to main content Accessibility help
×
Home
Hostname: page-component-5bf98f6d76-rs6k2 Total loading time: 0.269 Render date: 2021-04-21T15:20:23.183Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "metricsAbstractViews": false, "figures": false, "newCiteModal": false, "newCitedByModal": true }

Thermodynamics of nucleic acids and their interactions with ligands

Published online by Cambridge University Press:  16 January 2001

Andrew N. Lane
Affiliation:
Division of Molecular Science, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
Terence C. Jenkins
Affiliation:
Yorkshire Cancer Research Laboratory of Drug Design, Cancer Research Group, University of Bradford, Bradford, West Yorkshire BD7 1DP, UK

Abstract

1. Introduction 255

1.1 General thermodynamics 256

2. Nucleic acid thermodynamics 260

2.1 DNA duplexes 261

2.2 RNA duplexes 263

2.3 Hybrid DNA–RNA duplexes 264

2.4 Hydration 267

2.5 Conformational flexibility 269

2.6 Thermodynamics 272

3. Nucleic acid–ligand interactions 277

3.1 Minor groove binders 278

3.2 DNA intercalators 284

3.3 Triple-helical systems 288

3.3.1 Structures 288

3.3.2 Hydration 291

3.3.3 Thermodynamics 291

4. Conclusions 295

5. Acknowledgements 298

6. References 298

In recent years the availability of large quantities of pure synthetic DNA and RNA has revolutionised the study of nucleic acids, such that it is now possible to study their conformations, dynamics and large-scale properties, and their interactions with small ligands, proteins and other nucleic acids in unprecedented detail. This has led to the (re)discovery of higher order structures such as triple helices and quartets, and also the catalytic activity of RNA contingent on three-dimensional folding, and the extraordinary specificity possible with DNA and RNA aptamers.

Nucleic acids are quite different from proteins, even though they are both linear polymers formed from a small number of monomeric units. The major difference reflects the nature of the linkage between the monomers. The 5′–3′ phosphodiester linkage in nucleic acids carries a permanent negative charge, and affords a relatively large number of degrees of freedom, whereas the essentially rigid planar peptide linkage in proteins is neutral and provides only two degrees of torsional freedom per backbone residue. These two properties conspire to make nucleic acids relatively flexible and less likely to form extensive folded structures. Even when true 3D folded structures are formed from nucleic acids, the topology remains simple, with the anionic phosphates forming the surface of the molecule. Nevertheless, nucleic acids do occur in a variety of structures that includes single strands and high-order duplex, triplex or tetraplex (‘quadruplex’) forms. The principles of biological recognition and the related problem of understanding the forces that stabilise such folded structures are in some respects more straightforward than for proteins, making them attractive model systems for understanding general biophysical problems. This view is aided by the relatively facile chemical synthesis of pure nucleic acids of any desired size and defined sequence, and the ease of incorporation of a wide spectrum of chemically modified bases, sugars and backbone linkers. Such modifications are considerably more difficult to achieve with oligopeptides or proteins.

Type
Review Article
Copyright
© 2000 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below.

Full text views

Full text views reflects PDF downloads, PDFs sent to Google Drive, Dropbox and Kindle and HTML full text views.

Total number of HTML views: 20
Total number of PDF views: 97 *
View data table for this chart

* Views captured on Cambridge Core between September 2016 - 21st April 2021. This data will be updated every 24 hours.

Send article to Kindle

To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Thermodynamics of nucleic acids and their interactions with ligands
Available formats
×

Send article to Dropbox

To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

Thermodynamics of nucleic acids and their interactions with ligands
Available formats
×

Send article to Google Drive

To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

Thermodynamics of nucleic acids and their interactions with ligands
Available formats
×
×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *