Intermolecular ‘cross-torque’ : the N4-cytosine propargyl residue is rotated to the ‘CH’-edge as a result of Watson–Crick interaction

Autoren

Olwen Domingo
Isabell Hellmuth
Andres Jaeschke
Christoph Kreutz
Mark Helm

Autoren-URL

https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000357886900009&DestLinkType=FullRecord&DestApp=WOS_CPL

DOI

10.1093/nar/gkv285

eISSN

1362-4962

Externe Identifier

Clarivate Analytics Document Solution ID: CM7PJ
PubMed Identifier: 25934805

ISSN

0305-1048

Ausgabe der Veröffentlichung

11

Zeitschrift

NUCLEIC ACIDS RESEARCH

Paginierung

5275 - 5283

Datum der Veröffentlichung

2015

Status

Published

Titel

Intermolecular 'cross-torque': the <i>N<SUP>4</SUP></i>-cytosine propargyl residue is rotated to the 'CH'-edge as a result of Watson-Crick interaction

Sub types

Article

Ausgabe der Zeitschrift

43

Data source: Web of Science (Lite)

Autoren

O Domingo
I Hellmuth
A Jaschke
C Kreutz
M Helm

DOI

10.1093/nar/gkv285

eISSN

1362-4962

ISSN

0305-1048

Ausgabe der Veröffentlichung

11

Zeitschrift

Nucleic Acids Research

Sprache

en

Online publication date

2015

Paginierung

5275 - 5283

Datum der Veröffentlichung

2015

Status

Published

Herausgeber

Oxford University Press (OUP)

Herausgeber URL

http://dx.doi.org/10.1093/nar/gkv285

Datum der Datenerfassung

2019

Titel

Intermolecular 'cross-torque': the N4-cytosine propargyl residue is rotated to the 'CH'-edge as a result of Watson-Crick interaction

Ausgabe der Zeitschrift

43

Data source: Crossref

Abstract

Propargyl groups are attractive functional groups for labeling purposes, as they allow CuAAC-mediated bioconjugation. Their size minimally exceeds that of a methyl group, the latter being frequent in natural nucleotide modifications. To understand under which circumstances propargyl-containing oligodeoxynucleotides preserve base pairing, we focused on the exocyclic amine of cytidine. Residues attached to the exocyclic N4 may orient away from or toward the Watson-Crick face, ensuing dramatic alteration of base pairing properties. ROESY-NMR experiments suggest a uniform orientation toward the Watson-Crick face of N(4)-propargyl residues in derivatives of both deoxycytidine and 5-methyl-deoxycytidine. In oligodeoxynucleotides, however, UV-melting indicated that N(4)-propargyl-deoxycytidine undergoes standard base pairing. This implies a rotation of the propargyl moiety toward the 'CH'-edge as a result of base pairing on the Watson-Crick face. In oligonucleotides containing the corresponding 5-methyl-deoxycytidine derivative, dramatically reduced melting temperatures indicate impaired Watson-Crick base pairing. This was attributed to a steric clash of the propargyl moiety with the 5-methyl group, which prevents back rotation to the 'CH'-edge, consequently preventing Watson-Crick geometry. Our results emphasize the tendency of an opposing nucleic acid strand to mechanically rotate single N(4)-substituents to make way for Watson-Crick base pairing, providing no steric hindrance is present on the 'CH'-edge.

Addresses

Department of Pharmaceutical Chemistry, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, 55128 Mainz, Rhineland-Palatinate, Germany.

Autoren

Olwen Domingo
Isabell Hellmuth
Andres Jäschke
Christoph Kreutz
Mark Helm

DOI

10.1093/nar/gkv285

eISSN

1362-4962

Externe Identifier

PubMed Identifier: 25934805
PubMed Central ID: PMC4477647

Open access

true

ISSN

0305-1048

Ausgabe der Veröffentlichung

11

Zeitschrift

Nucleic acids research

Schlüsselwörter

Organophosphorus Compounds
Cytosine
Nucleosides
Oligodeoxyribonucleotides
Base Pairing
Rotation

Sprache

eng

Medium

Print-Electronic

Online publication date

2015

Open access status

Open Access

Paginierung

5275 - 5283

Datum der Veröffentlichung

2015

Status

Published

Publisher licence

CC BY

Datum der Datenerfassung

2015

Titel

Intermolecular 'cross-torque': the N4-cytosine propargyl residue is rotated to the 'CH'-edge as a result of Watson-Crick interaction.

Sub types

Research Support, Non-U.S. Gov't
research-article
Journal Article

Ausgabe der Zeitschrift

43

Files

https://academic.oup.com/nar/article-pdf/43/11/5275/3991242/gkv285.pdf https://europepmc.org/articles/PMC4477647?pdf=render

Data source: Europe PubMed Central

Abstract

Propargyl groups are attractive functional groups for labeling purposes, as they allow CuAAC-mediated bioconjugation. Their size minimally exceeds that of a methyl group, the latter being frequent in natural nucleotide modifications. To understand under which circumstances propargyl-containing oligodeoxynucleotides preserve base pairing, we focused on the exocyclic amine of cytidine. Residues attached to the exocyclic N4 may orient away from or toward the Watson-Crick face, ensuing dramatic alteration of base pairing properties. ROESY-NMR experiments suggest a uniform orientation toward the Watson-Crick face of N(4)-propargyl residues in derivatives of both deoxycytidine and 5-methyl-deoxycytidine. In oligodeoxynucleotides, however, UV-melting indicated that N(4)-propargyl-deoxycytidine undergoes standard base pairing. This implies a rotation of the propargyl moiety toward the 'CH'-edge as a result of base pairing on the Watson-Crick face. In oligonucleotides containing the corresponding 5-methyl-deoxycytidine derivative, dramatically reduced melting temperatures indicate impaired Watson-Crick base pairing. This was attributed to a steric clash of the propargyl moiety with the 5-methyl group, which prevents back rotation to the 'CH'-edge, consequently preventing Watson-Crick geometry. Our results emphasize the tendency of an opposing nucleic acid strand to mechanically rotate single N(4)-substituents to make way for Watson-Crick base pairing, providing no steric hindrance is present on the 'CH'-edge.

Date of acceptance

2015

Autoren

Olwen Domingo
Isabell Hellmuth
Andres Jäschke
Christoph Kreutz
Mark Helm

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/25934805

DOI

10.1093/nar/gkv285

eISSN

1362-4962

Externe Identifier

PubMed Central ID: PMC4477647

Ausgabe der Veröffentlichung

11

Zeitschrift

Nucleic Acids Res

Schlüsselwörter

Base Pairing
Cytosine
Nucleosides
Oligodeoxyribonucleotides
Organophosphorus Compounds
Rotation

Sprache

eng

Country

England

Paginierung

5275 - 5283

PII

gkv285

Datum der Veröffentlichung

2015

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2015

Titel

Intermolecular 'cross-torque': the N4-cytosine propargyl residue is rotated to the 'CH'-edge as a result of Watson-Crick interaction.

Sub types

Journal Article
Research Support, Non-U.S. Gov't

Ausgabe der Zeitschrift

43

Data source: PubMed

Author's licence

CC-BY

Autoren

Olwen Domingo
Isabell Hellmuth
Andres Jäschke
Christoph Kreutz
Mark Helm

Hosting institution

Universitätsbibliothek Mainz

Sammlungen

DFG-OA-Publizieren (2012 - 2017)

Resource version

Published version

DOI

10.1093/nar/gkv285

Funding acknowledgements

DFG, Open Access-Publizieren Universität Mainz / Universitätsmedizin

File(s) embargoed

false

Open access

true

ISSN

1362-4962

Ausgabe der Veröffentlichung

11

Zeitschrift

Nucleic acids research

Schlüsselwörter

500 Naturwissenschaften
500 Natural sciences and mathematics

Sprache

eng

Open access status

Open Access

Paginierung

5275 - 5283

Datum der Veröffentlichung

2015

Public URL

https://openscience.ub.uni-mainz.de/handle/20.500.12030/7818

Herausgeber

Oxford Univ. Press

Herausgeber URL

http://dx.doi.org/10.1093/nar/gkv285

Datum der Datenerfassung

2022

Datum, an dem der Datensatz öffentlich gemacht wurde

2022

Zugang

Public

Titel

Intermolecular ‘cross-torque’ : the N4-cytosine propargyl residue is rotated to the ‘CH’-edge as a result of Watson–Crick interaction

Ausgabe der Zeitschrift

43

Files

intermolecular_crosstorque___-20220913235609023.pdf

Data source: OPENSCIENCE.UB

Intermolecular ‘cross-torque’ : the N4-cytosine propargyl residue is rotated to the ‘CH’-edge as a result of Watson–Crick interaction

Files

Files

Tools