Orientation preferences of hairpin pyrrole-imidazole polyamides toward mCGG site.
Bioorg Med Chem
; 27(11): 2167-2171, 2019 06 01.
Article
in En
| MEDLINE
| ID: mdl-31000407
ABSTRACT
Hairpin pyrrole-imidazole (Py-Im) polyamides are promising medium-sized molecules that bind sequence-specifically to the minor groove of B-form DNA. Here, we synthesized a series of hairpin Py-Im polyamides and explored their binding affinities and orientation preferences to methylated DNA with the mCGG target sequence. Thermal denaturation assays revealed that the five hairpin Py-Im polyamides, which were anticipated to recognize mCGG in a forward orientation, bind to nontarget DNA, GGmC, in a reverse orientation. Therefore, we designed five Py-Im polyamides that could recognize mCGG in a reverse orientation. We found that the two Py-Im polyamides containing Im/ß pairs preferentially bound to mCGG in a reverse orientation. The reverse binding Py-Im polyamide successfully inhibited TET1 binding on the methylated DNA. Taken together, this study illustrated the importance of designing reverse binding Py-Im polyamides for the target sequence, mCGG, which paved the way for Py-Im polyamides that can be used with otherwise difficult to access DNA with CG sequences.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyrroles
/
DNA, B-Form
/
Imidazoles
/
Nylons
Language:
En
Journal:
Bioorg Med Chem
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2019
Type:
Article
Affiliation country:
Japan