Investigating the Effect of Chemical Modifications on the Ribose Sugar Conformation, Watson-Crick Base Pairing, and Intrastrand Stacking Interactions: A Theoretical Approach.
J Phys Chem B
; 128(35): 8313-8331, 2024 Sep 05.
Article
em En
| MEDLINE
| ID: mdl-39172066
ABSTRACT
Over the last few decades, chemically modified sugars have been incorporated into nucleic acid-based therapeutics to improve their pharmacological potential. Chemical modification can influence the sugar conformation, Watson-Crick hydrogen (W-C) bonding, and nucleobase stacking interactions, which play major roles in the structural integrity and dynamic properties of nucleic acid duplexes. In this study, we categorized 33 uridine (U*) and cytidine (C*) sugar modifications and calculated their sugar conformational parameters. We also calculated the Watson-Crick hydrogen bond energies of the modified RNA-type base pairs (U*A and C*G) using DFT and sSAPT0 methods. The W-C base pairing energy calculations suggested that the South-type modified sugar strengthens the C*G base pair and weakens the U*A base pair compared to the unmodified one. In contrast, the North-type sugar modifications form weaker C*G base pair and marginally stronger U*A base pair compared to the South-type modified sugars. Moreover, intrastrand base stacking energies were calculated for 15 modifications incorporated at the fourth position in 7-mer non-self-complementary RNA duplexes [(GCAU*GAC)2 and (GCAC*GAC)2], utilizing molecular dynamics simulation and quantum mechanical (DFT and sSAPT0) methods. The sugar modifications were found to have minimal effect on the intrastrand base-stacking interactions. However, the glycol nucleic acid modification disturbs the intrastrand base-stacking significantly, corroborating the experimental data.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ribose
/
Pareamento de Bases
/
Ligação de Hidrogênio
Idioma:
En
Revista:
J Phys Chem B
Assunto da revista:
QUIMICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Índia