Towards an Understanding of the Molecular Mechanisms of Variable Unnatural Base-Pair Behavior: A Biophysical Analysis of dNaM-dTPT3.

Base Pairing
biopolymers nucleic acids nucleobases synthetic biology thermodynamics

Journal

Chemistry (Weinheim an der Bergstrasse, Germany)
ISSN: 1521-3765
Titre abrégé: Chemistry
Pays: Germany
ID NLM: 9513783

Informations de publication

Date de publication:
07 Oct 2021
Historique:
received: 30 06 2021
pubmed: 13 8 2021
medline: 9 10 2021
entrez: 12 8 2021
Statut: ppublish

Résumé

The series of unnatural base pairs (UBPs) developed by the Romesberg lab, which pair via hydrophobic and packing interactions have been replicated, transcribed, and translated inside of a living organism. However, as to why these UBPs exhibit variable fidelity and efficiency when used in different contexts is not clear. In an effort to gain some insights, we investigated the thermal stability and pairing selectivity of the (d)NaM-(d)TPT3 UBP in 11nt duplexes via UV spectroscopy and the effects on helical structure via CD spectroscopy. We observed that while the duplexes containing a UBP are less stable than fully natural duplexes, they are generally more stable than duplexes containing natural mispairs. This work provides the first insights connecting the thermal stability of the (d)NaM-(d)TPT3 UBP to the molecular mechanisms for varying replication fidelity in different sequence contexts in DNA, asymmetrical transcription fidelity, and codon:anticodon interactions and can assist in future UBP development.

Identifiants

DOI: 10.1002/chem.202102348 PMID: 34382264
pubmed: 34382264
doi: 10.1002/chem.202102348
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

13991-13997

Subventions

Organisme : national science foundation
ID : DGE-1346837
Organisme : national science foundation
ID : CHE-1504217
Organisme : foundation for the national institutes of health
ID : GM128376

Informations de copyright

© 2021 Wiley-VCH GmbH.

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Auteurs

Rebekah J Karadeema (RJ)

Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037.

Sydney E Morris (SE)

Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037.

Luke L Lairson (LL)

Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037.
ORCID: 0000-0001-6701-996X

Ramanarayanan Krishnamurthy (R)

Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037.
ORCID: 0000-0001-5238-610X

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Classifications MeSH

questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Conformation d'acide nucléique › Appariement de bases › Towards an Understanding of the Molecular...