Sequence-specific recognition of double-stranded DNA by synthetic minor groove binder conjugates. toward the construction of artificial site-specific deoxyribonucleases.
Bis-conjugates of hairpin N-methylpyrrole/N-methylimidazole oligocarboxamide minor groove binders (MGB) possessing enhanced affinity and sequence-specificity for dsDNA were synthesized. Two hairpin MGBs were connected by their N-termini via an aminodiacetate linker. The binding of bis-MGB conjugates to the target DNA was studied by gel mobility retardation, footprinting, and circular dichroism; their affinity and binding mode in the DNA minor groove were determined. In order to functionalize the bis-MGB conjugates, DNA-cleaving agents such as phenanthroline or bipyridine were attached. Effective site-specific cleavage of target DNA in the presence of Cu(2+) ions was observed.
Boutorine
Alexandre S
AS
Muséum National d'Histoire Naturelle, INSERM U565, Paris, France. alexandre.boutorine@mnhn.fr
Halby
Ludovic
L
Simon
Philippe
P
Perrouault
Loïc
L
Giovannangeli
Carine
C
Gursky
Georgy V
GV
Surovaya
Anna N
AN
Grokhovsky
Sergueï L
SL
Ryabinin
Vladimir A
VA
Sinyakov
Alexandre N
AN
D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry*; D003851:Deoxyribonucleases / Q000737:chemistry*; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D010618:Phenanthrolines / Q000737:chemistry; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry*; D016337:RNA, Catalytic / Q000138:chemical synthesis / Q000737:chemistry*
D007093:Imidazoles; D010618:Phenanthrolines; D011758:Pyrroles; D016337:RNA, Catalytic; D004247:DNA; D003851:Deoxyribonucleases; C096654:N-methylpyrrole