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In the same year as the discovery of the Sanger sequencing method, another group of scientists, Allan Maxam and Walter Gilbert, demonstrated their chemical-cleavage method for DNA sequencing. The Maxam-Gilbert method relies on using different chemicals that can cleave the DNA sequence at specific sites, the separation of resulting DNA fragments of variable size using electrophoresis, and deciphering the DNA sequence from the resulting gel bands.
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Updated: May 22, 2026

DNA Sequence Recognition by DNA Primase Using High-Throughput Primase Profiling

DNA Sequence Recognition by DNA Primase Using High-Throughput Primase Profiling

Published on: October 8, 2019

Subtle recognition of 14-base pair DNA sequences via threading polyintercalation.

Amy Rhoden Smith¹, Brian A Ikkanda, Garen G Holman

¹Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, Texas 78712, United States.

|May 5, 2012

Summary

New DNA-binding molecules called threading polyintercalators show promise as therapeutic agents. These molecules can distinguish between DNA sequences that differ by only one or two base pairs, offering precise gene expression control.

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Sequence-specific and Selective Recognition of Double-stranded RNAs over Single-stranded RNAs by Chemically Modified Peptide Nucleic Acids

Sequence-specific and Selective Recognition of Double-stranded RNAs over Single-stranded RNAs by Chemically Modified Peptide Nucleic Acids

Published on: September 21, 2017

Area of Science:

Medicinal Chemistry
Molecular Biology
Genetics

Background:

Small molecules that bind DNA sequence-specifically hold potential as antibiotics, antivirals, and anticancer agents by modulating gene expression.
Threading polyintercalators, based on 1,4,5,8-naphthalene diimide (NDI) units linked by peptides, are being developed for DNA binding applications.

Purpose of the Study:

To design and synthesize novel NDI-based tetraintercalators with modified DNA-binding modules.
To evaluate the DNA sequence discrimination capabilities and binding kinetics of these new compounds.

Main Methods:

Synthesis of new NDI-based tetraintercalators featuring altered major and minor groove-binding modules.
DNase I footprinting assays to determine DNA binding sites.
Kinetic analyses to measure binding affinities and dissociation rates.

Main Results:

The newly developed tetraintercalators exhibit significant discrimination (up to 30-fold) for 14 bp DNA sequences differing by only 1 or 2 base pairs.
DNA-binding affinities strongly correlate with dissociation rates.
The presence of C(2) symmetry in the DNA-binding molecules enhances association rates.

Conclusions:

Novel NDI-based tetraintercalators demonstrate high sequence specificity and discrimination capabilities for DNA binding.
These findings support the potential of threading polyintercalators as precise gene-targeting therapeutic agents.