“…DAPI preferentially binds in the minor groove of double-stranded DNA (dsDNA) with a high AT content. This DNA binding mode has been evidenced by crystallography, NMR data, spectroscopy, and molecular modeling, showing a stable minor-groove binding on (AT) sites of dsDNA. − As previously reported by different groups, this interaction mechanism produces drastic changes in the (chir)optical properties of DAPI. ,, Besides the enhancement of fluorescence of DAPI upon binding, another important consequence is the appearance of an induced circular dichroism (ICD), i.e., the achiral DAPI acquires a circular dichroism signal when bound to the chiral DNA. This ICD signal is observed at the level of a single DAPI bound in the minor groove at a central AATT sequence of short (dodecamer) dsDNA, and it varies with the length and the sequence of the (AT) tract on longer dsDNA .…”
Section: Introductionmentioning
confidence: 62%
“…To that aim, we investigate in depth the binding of DAPI to a double-stranded DNA with a model (AT) sequence, through a joint theoretical and experimental approach. This sequence has been selected since it is well-established that DAPI binds to the minor groove on (AT) sequences, whereas an intercalation binding mode could occur on (GC) sequences, which is still controversial. − , Besides, a previous study on the interaction between DAPI and single-strand oligonucleotides showed that DAPI interact with sequence containing (AAT) as trinucleotide repeating unit, by favoring the folding of the single strand into a hairpin structure with minor groove binding . In our spectroscopy experiments, we exploited a sequence of 23 base pairs (bp), for which multiple DAPIs can bind in the DNA minor groove.…”
Induced circular dichroism (ICD) of DNA-binding ligands is well known to be strongly influenced by the specific mode of binding, but the relative importance of the possible mechanisms has remained undetermined. With a combination of molecular dynamics simulations, CD response calculations, and experiments on an AT-sequence, we show that the ICD of minor-groove-bound 4',6-diamidino-2-phenylindole (DAPI) originates from an intricate interplay between the chiral imprint of DNA, off-resonant excitonic coupling to nucleobases, charge-transfer, and resonant excitonic coupling between DAPIs. The significant contributions from charge-transfer and the chiral imprint to the ICD demonstrate the inadequacy of a standard Frenkel exciton theory of the DAPI-DNA interactions.
“…DAPI preferentially binds in the minor groove of double-stranded DNA (dsDNA) with a high AT content. This DNA binding mode has been evidenced by crystallography, NMR data, spectroscopy, and molecular modeling, showing a stable minor-groove binding on (AT) sites of dsDNA. − As previously reported by different groups, this interaction mechanism produces drastic changes in the (chir)optical properties of DAPI. ,, Besides the enhancement of fluorescence of DAPI upon binding, another important consequence is the appearance of an induced circular dichroism (ICD), i.e., the achiral DAPI acquires a circular dichroism signal when bound to the chiral DNA. This ICD signal is observed at the level of a single DAPI bound in the minor groove at a central AATT sequence of short (dodecamer) dsDNA, and it varies with the length and the sequence of the (AT) tract on longer dsDNA .…”
Section: Introductionmentioning
confidence: 62%
“…To that aim, we investigate in depth the binding of DAPI to a double-stranded DNA with a model (AT) sequence, through a joint theoretical and experimental approach. This sequence has been selected since it is well-established that DAPI binds to the minor groove on (AT) sequences, whereas an intercalation binding mode could occur on (GC) sequences, which is still controversial. − , Besides, a previous study on the interaction between DAPI and single-strand oligonucleotides showed that DAPI interact with sequence containing (AAT) as trinucleotide repeating unit, by favoring the folding of the single strand into a hairpin structure with minor groove binding . In our spectroscopy experiments, we exploited a sequence of 23 base pairs (bp), for which multiple DAPIs can bind in the DNA minor groove.…”
Induced circular dichroism (ICD) of DNA-binding ligands is well known to be strongly influenced by the specific mode of binding, but the relative importance of the possible mechanisms has remained undetermined. With a combination of molecular dynamics simulations, CD response calculations, and experiments on an AT-sequence, we show that the ICD of minor-groove-bound 4',6-diamidino-2-phenylindole (DAPI) originates from an intricate interplay between the chiral imprint of DNA, off-resonant excitonic coupling to nucleobases, charge-transfer, and resonant excitonic coupling between DAPIs. The significant contributions from charge-transfer and the chiral imprint to the ICD demonstrate the inadequacy of a standard Frenkel exciton theory of the DAPI-DNA interactions.
“…Small molecules recognizing specific DNA sequences have attracted great interest for gene-targeted drugs, which may alter the local structure of DNA to inhibit access of activators or repressors to regulate ultimate gene expression processes . A number of clinically useful drugs such as distamycin A ( 1 ), 4,6-diamidino-2-phenylindole (DAPI) ( 2 ), 2f-g, echinomycin ( 3 ), actinomycin D, 2b-d, and cisplatin interact with DNA in various fashions via hydrophobic, electrostatic, hydrogen-bonding, dipolar forces and/or coordinate interactions. Of these, distamycin A ( 1 ) and DAPI ( 2 ) are minor groove binders that recognize AT-rich regions.…”
Section: Introductionmentioning
confidence: 99%
“…Of these, distamycin A ( 1 ) and DAPI ( 2 ) are minor groove binders that recognize AT-rich regions. They simultaneously bind to adenine N(3) and thymine O(2) by hydrogen bondings and stabilize the A−T duplex structure (Scheme ). , Currently, chemical modification of these minor groove binders has been actively undertaken 1 2 …”
DNase I footprinting has revealed that zinc(II) complexes with macrocyclic tetraamines (1,4,7,10-tetraazacyclododecane,cyclen) appended with one or two aryl-methyl group(s), ((9-acridinyl)methyl-, (4-quinolyl)methyl-, 1,7-bis(4-quinolyl)methyl-, (1-naphthyl)methyl-, and 1,7-bis(1-naphthyl)methyl-cyclen)
selectively bind to native double-stranded DNA (150 base pairs), at AT-rich regions like classical minor groove
binders (distamycin A and 4,6-diamidino-2-phenylindole (DAPI)). The selectivity and affinity depend on the
stacking ability and number of the aromatic ring. Zn2+ is an essential metal ion for the DNA binding, which
cannot be replaced by other metal ions such as Cu2+ or Ni2+. The DNA binding by these Zn2+−cyclen derivatives
was inhibited by captopril having a stronger affinity for the fifth coordination site of the Zn2+−cyclen complexes.
Micrococcal nuclease footprinting, moreover, revealed that those Zn2+−cyclen derivatives bound only to the
thymine groups in the A−T base pairs, while distamycin A and DAPI simultaneously bound to the thymine
and adenine groups in the A−T base pairs. Distamycin A and the Zn2+−(4-quinolyl)methyl-cyclen reversibly
competed for common AT-rich regions of minor groove. The DNA binding mode by the Zn2+−cyclen
derivatives was due to the selective and strong complex formation between the Zn2+−cyclen moiety and the
imide-deprotonated thymine at neutral pH.
“…4′,6-Diamidino-2-phenylindole (DAPI) is a minor groove binder − molecule and other groove binder molecules are able to displace DAPI from the DAPI–DNA complex.…”
Binding of Nile Blue (NB) with calf thymus DNA has been studied using molecular modeling, spectroscopic, and thermodynamic techniques. Our study revealed that NB binds to the DNA helix by two types of modes (groove binding and intercalation) simultaneously. The thermodynamic study showed that the overall binding free energy is a combination of several negative and positive free energy changes. The binding was favored by negative enthalpy and positive entropy changes (due to the release of water from the DNA helix). The docking study validated all experimental evidence and showed that NB binds to a DNA minor groove at low concentrations and switches to intercalation mode at higher concentrations.
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