Substituent effects on indole universal bases in DNA
Avi Benitah1, Dominic F Qualley1, Stephen A Woski1
1Department of Chemistry & Biochemistry, The University of Alabama, Tuscaloosa, AL, USA.
Nucleosides, Nucleotides & Nucleic Acids
|August 3, 2022
Summary
Researchers synthesized novel indole nucleosides for DNA applications. These modified nucleosides show enhanced stability and universal base properties, advancing synthetic biology and genetic research.
Area of Science:
- Biochemistry
- Organic Chemistry
- Molecular Biology
Background:
- Oligodeoxynucleotides are crucial in molecular biology and synthetic biology.
- The development of universal bases is key to expanding DNA applications.
- Indole nucleosides offer potential as non-natural DNA components.
Purpose of the Study:
- To synthesize and evaluate eleven 5-substituted-indole nucleoside residues.
- To assess the universal base properties of these novel residues in DNA duplexes.
- To understand the relationship between indole substituents and DNA complex stability.
Main Methods:
- Synthesis of eleven 5-substituted-indole nucleoside analogs.
- Incorporation of these analogs into 15-mer oligodeoxynucleotide duplexes.
- UV thermal denaturation experiments to determine duplex stability.
Main Results:
- All synthesized substituted indoles demonstrated greater stability than unsubstituted indole.
- Electronic properties of substituents on the indole ring correlated with duplex stability.
- Some residues exhibited broader base-pairing promiscuity than the 5-nitroindole control.
Conclusions:
- 5-substituted-indole nucleosides represent a promising class of universal bases for DNA.
- Substituent electronic effects significantly influence the stability of DNA duplexes containing these residues.
- Further research is needed to clarify the precise relationship between substituents and base-pairing selectivity.
More Related Videos
09:33Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
Published on: March 20, 2018
13.9K
07:44Synthesis of Wavelength-shifting DNA Hybridization Probes by Using Photostable Cyanine Dyes
Published on: July 6, 2016
11.3K
Related Concept Videos
01:09Directing Effect of Substituents: meta-Directing Groups
4.9K
Substituents on the benzene ring that direct an incoming electrophile to undergo substitution at the meta position are called meta directors. All meta directors either have a positive charge on the atom directly bonded to the ring or a partial positive charge. These groups function by withdrawing electrons from the ring through inductive and resonance effects. Consider the carbocation intermediates formed upon the addition of an electrophile on nitrobenzene at the...
4.9K
02:27DNA Base Pairing
28.0K
Erwin Chargaff’s rules on DNA equivalence paved the way for the discovery of base pairing in DNA. Chargaff’s rules state that in a double-stranded DNA molecule,
28.0K
01:14Directing Effect of Substituents: ortho–para-Directing Groups
6.8K
Ortho–para directors are substituent groups attached to the benzene ring and direct the addition of an electrophile to the positions ortho or para to the substituent. All electron-donating groups are considered ortho–para directors. They donate electrons to the ring and make the ring more electron-rich. The ring is therefore susceptible to the addition of electrophiles. Substituents such as amino, hydroxy, or alkoxy, containing lone pairs on the atom adjacent to the ring, donate...
6.8K
01:18Basicity of Aromatic Amines
7.3K
The basicity of aromatic amines is much weaker than that of aliphatic amines due to the involvement of the lone pair of electrons over the N atom in resonance with the aryl rings. Generally, the electron-donating ability of any substituents on the aryl ring of aromatic amines increases the basicity of the amine by increasing electron density, and hence the availability of lone pair on the nitrogen. On the other hand, electron-withdrawing functional groups on the aryl ring of amines decrease the...
7.3K
02:34Nucleophilic Substitution Reactions
16.8K
Historical perspective
In 1896, the German chemist Paul Walden discovered that he could interconvert pure enantiomeric (+) and (-) malic acids through a series of reactions. This conversion suggested the involvement of optical inversion during the substitution reaction. Further, in 1930, Sir Christopher Ingold described for the first time two different forms of nucleophilic substitution reactions, which are known as SN1 (nucleophilic substitution unimolecular) and SN2 (nucleophilic substitution...
In 1896, the German chemist Paul Walden discovered that he could interconvert pure enantiomeric (+) and (-) malic acids through a series of reactions. This conversion suggested the involvement of optical inversion during the substitution reaction. Further, in 1930, Sir Christopher Ingold described for the first time two different forms of nucleophilic substitution reactions, which are known as SN1 (nucleophilic substitution unimolecular) and SN2 (nucleophilic substitution...
16.8K
01:30Spontaneous and Induced Mutations
126
Spontaneous mutations arise infrequently during DNA replication due to errors in the process. A key factor behind these errors is tautomeric shifts in nitrogenous bases, where bases transition from keto to enol forms or amino to imino forms. This shift can alter base-pairing rules, leading to mutations. Additionally, reactive oxygen species (ROS) arising from aerobic metabolism can damage DNA, resulting in depurination (loss of a purine base) or depyrimidination (loss of a pyrimidine base).
126