Cyclic mismatch binding ligand CMBL4 binds to the 5'-T-3'/5'-GG-3' site by inducing the flipping out of thymine base.

Abstract:

:A newly designed cyclic bis-naphthyridine carbamate dimer CMBL4: with a limited conformational flexibility was synthesized and characterized. Absorption spectra revealed that two naphthyridines in CMBL4: were stacked on each other in aqueous solutions. The most efficient binding of CMBL4: to DNA was observed for the sequence 5'-T-3'/5'-GG-3' (T/GG) with the formation of a 1:1 complex, which is one of possible structural elements involved in the higher order structures of (TGG)n repeat DNA triggering the genome microdeletion. Surface plasmon resonance assay also showed the binding of CMBL4: with TGG repeat DNA. Potassium permanganate oxidation studies of CMBL4: -bound duplex containing the T/GG site showed that the CMBL4: -binding accelerated the oxidation of thymine at that site, which suggests the flipping out of the thymine base from a π-stack. Preferential binding was observed for CMBL4: compared with its acyclic variants, which suggests the marked significance of the macrocyclic structure for the recognition of the T/GG site.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Mukherjee S,Dohno C,Asano K,Nakatani K

doi

10.1093/nar/gkw672

subject

Has Abstract

pub_date

2016-09-06 00:00:00

pages

7090-9

issue

15

eissn

0305-1048

issn

1362-4962

pii

gkw672

journal_volume

44

pub_type

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