KRAS Promoter G-Quadruplexes from Sequences of Different Length: A Physicochemical Study.
Int J Mol Sci
; 22(1)2021 Jan 05.
Article
em En
| MEDLINE
| ID: mdl-33466280
ABSTRACT
DNA G-quadruplexes (G4s) form in relevant genomic regions and intervene in several biological processes, including the modulation of oncogenes expression, and are potential anticancer drug targets. The human KRAS proto-oncogene promoter region contains guanine-rich sequences able to fold into G4 structures. Here, by using circular dichroism and differential scanning calorimetry as complementary physicochemical methodologies, we compared the thermodynamic stability of the G4s formed by a shorter and a longer version of the KRAS promoter sequence, namely 5'-AGGGCGGTGTGGGAATAGGGAA-3' (KRAS 22RT) and 5'-AGGGCGGTGTGGGAAGAGGGAAGAGGGGGAGG-3' (KRAS 32R). Our results show that the unfolding mechanism of KRAS 32R is more complex than that of KRAS 22RT. The different thermodynamic stability is discussed based on the recently determined NMR structures. The binding properties of TMPyP4 and BRACO-19, two well-known G4-targeting anticancer compounds, to the KRAS G4s were also investigated. The present physicochemical study aims to help in choosing the best G4 target for potential anticancer drugs.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas p21(ras)
/
Regiões Promotoras Genéticas
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article