Effects of guanine bases at the central loop on stabilization of the quadruplex DNAs and their interactions with Meso-tetrakis(N-methylpyridium-4-yl)porphyrin

Autor: Seog K. Kim, Jihye Moon, Myung Won Lee, Sun Hee Jeon
Rok vydání: 2015
Předmět:
Zdroj: Biophysical chemistry. 205
ISSN: 1873-4200
Popis: The thermal stability of the G-quadruplex formed from the thrombin-binding aptamer, 5′G 2 T 2 G 2 TGTG 2 T 2 G 2 , in which the guanine (G) base at the central loop was replaced with an adenine (A) or inosine (I) base, was examined to determine the role of the central G base in stabilizing the quadruplex. Replacement of the central G base by the I base resulted in a slight decrease in thermal stability. On the other hand, the stability of the G-quadruplex decreased to a significant extent when it was replaced with the A base. The optimized structure of the G-quadruplex, which was obtained by a molecular dynamic simulation, showed that the carbonyl group of the C5 position of the central G base could form hydrogen bonds with the G1 amine group at the C7 position on the upper G-quartet. This formation of a hydrogen bond contributes to the stability of the G-quadruplex. The spectral property of meso -tetrakis( N -methylpyridium-4yl)porphyrin (TMPyP) associated with the G-quadruplex was characterized by a moderate red shift and hypochromism in the absorption spectrum, a positive CD signal, and two emission maxima in the fluorescence emission spectrum, suggesting that TMPyP binds at the exterior of the G-quadruplex. Spectral properties were slightly altered when the G base at the central loop was replaced with A or I, while the fluorescence decay times of TMPyP associated with the G-quadruplex were identical. Observed spectral properties removes the possibility of intercalation binding mode for TMPyP. TMPyP binds at the exterior of the quadruplex. Whether it stacks on the central loop or binds at the side of the quadruplex is unclear at this stage.
Databáze: OpenAIRE