DNA recognition by quinoline antibiotics: use of base-modified DNA molecules to investigate determinants of sequence-specific binding of luzopeptin.
The luzopeptin antibiotics contain a cyclic decadepsipeptide to which are attached two quinoline chromophores that bisintercalate into DNA. Although they bind DNA less tightly than the structurally related quinoxaline antibiotics echinomycin and triostin A, the molecular basis of their interaction remains unclear. We have used the PCR in conjunction with novel nucleotides to create specifically modified DNA for footprinting experiments. In order to study the influence that removal, addition or relocation of the guanine 2-amino group, which normally identifies G.C base pairs from the minor groove, has on the interaction of luzopeptin antibiotics with DNA. The presence of a purine 2-amino group is not strictly required for binding of luzopeptin to DNA, but the exact location of this group can alter the position of preferred drug binding sites. It is, however, not the sole determinant of nucleotide sequence recognition in luzopeptin-DNA interaction. Nor can the selectivity of luzopeptin be attributed to the quinoline chromophores, suggesting that an analogue mode of DNA recognition may be operative. This is in contrast to the digital readout that seems to predominate with the quinoxaline antibiotics.
Bailly
C
C
INSERM U-524 et Laboratoire de Pharmacologie Antitumorale du Centre Oscar Lambret, IRCL, Lille, France.
Crow
S
S
Minnock
A
A
Waring
M J
MJ
D015075:2-Aminopurine / Q000031:analogs & derivatives* / Q000737:chemistry; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D020029:Base Pairing; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry; D018983:DNA Footprinting; D004261:DNA Replication / Q000187:drug effects; D004269:DNA, Bacterial / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000378:metabolism; D004448:Echinomycin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D006860:Hydrogen Bonding; D006912:Hydroxyquinolines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D007288:Inosine / Q000737:chemistry; D007364:Intercalating Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011804:Quinolines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011810:Quinoxalines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship; D047630:Depsipeptides
D015075:2-Aminopurine; D000981:Antiprotozoal Agents; D004247:DNA; D004269:DNA, Bacterial; D003850:Deoxyribonuclease I; D004448:Echinomycin; D006912:Hydroxyquinolines; D007288:Inosine; D007364:Intercalating Agents; D010456:Peptides, Cyclic; D011804:Quinolines; D011810:Quinoxalines; C068640:luzopeptin-DNA complex; C031945:triostin A; C007300:2,6-diaminopurine; C029831:luzopeptins; D047630:Depsipeptides