Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Phosphate backbone neutralization increases duplex DNA flexibility: a model for protein binding.

Tamara M Okonogi1, Stephen C Alley, Eric A Harwood

  • 1Department of Chemistry, Box 351700, University of Washington, Seattle, WA 98195-1700, USA.

Proceedings of the National Academy of Sciences of the United States of America
|April 4, 2002
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

First-generation and preclinical evaluation of an EphA5-targeted antibody-drug conjugate in solid tumors.

The Journal of clinical investigation·2025
Same author

A modelling approach to compare ADC deconjugation and systemic elimination rates of individual drug-load species using native ADC LC-MS data from human plasma.

Xenobiotica; the fate of foreign compounds in biological systems·2024
Same author

Mechanistic Modeling of Central Nervous System Pharmacokinetics and Target Engagement of HER2 Tyrosine Kinase Inhibitors to Inform Treatment of Breast Cancer Brain Metastases.

Clinical cancer research : an official journal of the American Association for Cancer Research·2022
Same author

2021 White Paper on Recent Issues in Bioanalysis: Mass Spec of Proteins, Extracellular Vesicles, CRISPR, Chiral Assays, Oligos; Nanomedicines Bioanalysis; ICH M10 Section 7.1; Non-Liquid & Rare Matrices; Regulatory Inputs (<u>Part 1A</u> - Recommendations on Endogenous Compounds, Small Molecules, Complex Methods, Regulated Mass Spec of Large Molecules, Small Molecule, PoC & <u>Part 1B</u> - Regulatory Agencies' Inputs on Bioanalysis, Biomarkers, Immunogenicity, Gene & Cell Therapy and Vaccine).

Bioanalysis·2022
Same author

Elimination of tucatinib, a small molecule kinase inhibitor of HER2, is primarily governed by CYP2C8 enantioselective oxidation of gem-dimethyl.

Cancer chemotherapy and pharmacology·2022
Same author

Design and synthesis of chromophores with enhanced electro-optic activities in both bulk and plasmonic-organic hybrid devices.

Materials horizons·2021
Same journal

In This Issue.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Long-term cultural continuity across the Neanderthal-modern human sequence at Üçağızlı II Cave, northern Levant.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Dolphins use names to remember whom to avoid.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Retraction for Shaked and Frenkel, Curiouser and curiouser: Meningeal lymphoid structures in the aging brain.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Small but mighty: The outsized role of small water bodies in the global carbon cycle.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Functional traits produce conditional outcomes in different community contexts.

Proceedings of the National Academy of Sciences of the United States of America·2026
See all related articles

Replacing DNA phosphates with neutral methylphosphonates increases DNA flexibility, aiding protein-DNA recognition. This finding reveals a new mechanism in how proteins bind to DNA.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Structural Biology

Background:

  • Protein-DNA recognition involves charge neutralization of DNA phosphates and DNA bending.
  • Methylphosphonate substitutions serve as a model for protein-induced DNA bending.
  • The impact of charge neutralization on DNA's inherent flexibility remains unexplored.

Purpose of the Study:

  • To investigate the effect of methylphosphonate substitutions on DNA flexibility.
  • To quantify the change in local DNA flexibility upon backbone neutralization.
  • To understand how altered DNA flexibility contributes to protein-DNA interactions.

Main Methods:

  • Development of a novel method to measure differential flexibility of duplex DNA.
  • Incorporation of methylphosphonate substitutions into DNA duplexes.

Related Experiment Videos

  • Comparative analysis of flexibility in modified versus unmodified DNA segments.

    • Main Results:

    • Methylphosphonate substitutions significantly increase local DNA flexibility, up to 40%.
    • Backbone neutralization alters the inherent mechanical properties of the DNA duplex.
    • This increased flexibility is a previously uncharacterized feature of modified DNA.

    Conclusions:

    • Backbone neutralization-dependent DNA flexibility is a key factor augmenting DNA-binding motifs.
    • Altered DNA flexibility plays a significant role in protein-DNA recognition processes.
    • This study provides new insights into the biophysical mechanisms governing protein-DNA interactions.