Large, sequence-dependent effects on DNA conformation by minor groove binding compounds

Denise S. Tevis, Arvind Kumar, Chad E. Stephens, David W. Boykin, W. David Wilson

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

To determine what topological changes antiparasitic heterocyclic dications can have on kinetoplast DNA, we have constructed ligation ladders, with phased A5 and ATATA sequences in the same flanking sequence context, as models. Bending by the A5 tract is observed, as expected, while the ATATA sequence bends DNA very little. Complexes of these DNAs with three diamidines containing either furan, thiophene or selenophene groups flanked by phenylamidines were investigated along with netropsin. With the bent A5 ladder the compounds caused either a slight increase or decrease in the bending angle. Surprisingly, however, with ATATA all of the compounds caused significant bending, to values close to or even greater than the A5 bend angle. Results with a mixed cis sequence, which has one A5 and one ATATA, show that the compounds bend ATATA in the same direction as a reference A5 tract, that is, into the minor groove. These results are interpreted in terms of a groove structure for A5 which is largely pre-organized for a fit to the heterocyclic amidines. With ATATA the groove is intrinsically wider and must close to bind the compounds tightly. The conformational change at the binding site then leads to significant bending of the alternating DNA sequence.

Original languageEnglish (US)
Article numbergkp558
Pages (from-to)5550-5558
Number of pages9
JournalNucleic Acids Research
Volume37
Issue number16
DOIs
StatePublished - Jul 3 2009
Externally publishedYes

Fingerprint

Nucleic Acid Conformation
Netropsin
Kinetoplast DNA
Amidines
Pentamidine
Antiparasitic Agents
Thiophenes
Ligation
Binding Sites
DNA
furan
Direction compound

ASJC Scopus subject areas

  • Genetics

Cite this

Large, sequence-dependent effects on DNA conformation by minor groove binding compounds. / Tevis, Denise S.; Kumar, Arvind; Stephens, Chad E.; Boykin, David W.; Wilson, W. David.

In: Nucleic Acids Research, Vol. 37, No. 16, gkp558, 03.07.2009, p. 5550-5558.

Research output: Contribution to journalArticle

Tevis, Denise S. ; Kumar, Arvind ; Stephens, Chad E. ; Boykin, David W. ; Wilson, W. David. / Large, sequence-dependent effects on DNA conformation by minor groove binding compounds. In: Nucleic Acids Research. 2009 ; Vol. 37, No. 16. pp. 5550-5558.
@article{cd7b8f54b5754367b5f49b2fb5d1f5ac,
title = "Large, sequence-dependent effects on DNA conformation by minor groove binding compounds",
abstract = "To determine what topological changes antiparasitic heterocyclic dications can have on kinetoplast DNA, we have constructed ligation ladders, with phased A5 and ATATA sequences in the same flanking sequence context, as models. Bending by the A5 tract is observed, as expected, while the ATATA sequence bends DNA very little. Complexes of these DNAs with three diamidines containing either furan, thiophene or selenophene groups flanked by phenylamidines were investigated along with netropsin. With the bent A5 ladder the compounds caused either a slight increase or decrease in the bending angle. Surprisingly, however, with ATATA all of the compounds caused significant bending, to values close to or even greater than the A5 bend angle. Results with a mixed cis sequence, which has one A5 and one ATATA, show that the compounds bend ATATA in the same direction as a reference A5 tract, that is, into the minor groove. These results are interpreted in terms of a groove structure for A5 which is largely pre-organized for a fit to the heterocyclic amidines. With ATATA the groove is intrinsically wider and must close to bind the compounds tightly. The conformational change at the binding site then leads to significant bending of the alternating DNA sequence.",
author = "Tevis, {Denise S.} and Arvind Kumar and Stephens, {Chad E.} and Boykin, {David W.} and Wilson, {W. David}",
year = "2009",
month = "7",
day = "3",
doi = "10.1093/nar/gkp558",
language = "English (US)",
volume = "37",
pages = "5550--5558",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "16",

}

TY - JOUR

T1 - Large, sequence-dependent effects on DNA conformation by minor groove binding compounds

AU - Tevis, Denise S.

AU - Kumar, Arvind

AU - Stephens, Chad E.

AU - Boykin, David W.

AU - Wilson, W. David

PY - 2009/7/3

Y1 - 2009/7/3

N2 - To determine what topological changes antiparasitic heterocyclic dications can have on kinetoplast DNA, we have constructed ligation ladders, with phased A5 and ATATA sequences in the same flanking sequence context, as models. Bending by the A5 tract is observed, as expected, while the ATATA sequence bends DNA very little. Complexes of these DNAs with three diamidines containing either furan, thiophene or selenophene groups flanked by phenylamidines were investigated along with netropsin. With the bent A5 ladder the compounds caused either a slight increase or decrease in the bending angle. Surprisingly, however, with ATATA all of the compounds caused significant bending, to values close to or even greater than the A5 bend angle. Results with a mixed cis sequence, which has one A5 and one ATATA, show that the compounds bend ATATA in the same direction as a reference A5 tract, that is, into the minor groove. These results are interpreted in terms of a groove structure for A5 which is largely pre-organized for a fit to the heterocyclic amidines. With ATATA the groove is intrinsically wider and must close to bind the compounds tightly. The conformational change at the binding site then leads to significant bending of the alternating DNA sequence.

AB - To determine what topological changes antiparasitic heterocyclic dications can have on kinetoplast DNA, we have constructed ligation ladders, with phased A5 and ATATA sequences in the same flanking sequence context, as models. Bending by the A5 tract is observed, as expected, while the ATATA sequence bends DNA very little. Complexes of these DNAs with three diamidines containing either furan, thiophene or selenophene groups flanked by phenylamidines were investigated along with netropsin. With the bent A5 ladder the compounds caused either a slight increase or decrease in the bending angle. Surprisingly, however, with ATATA all of the compounds caused significant bending, to values close to or even greater than the A5 bend angle. Results with a mixed cis sequence, which has one A5 and one ATATA, show that the compounds bend ATATA in the same direction as a reference A5 tract, that is, into the minor groove. These results are interpreted in terms of a groove structure for A5 which is largely pre-organized for a fit to the heterocyclic amidines. With ATATA the groove is intrinsically wider and must close to bind the compounds tightly. The conformational change at the binding site then leads to significant bending of the alternating DNA sequence.

UR - http://www.scopus.com/inward/record.url?scp=70449719309&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70449719309&partnerID=8YFLogxK

U2 - 10.1093/nar/gkp558

DO - 10.1093/nar/gkp558

M3 - Article

C2 - 19578063

AN - SCOPUS:70449719309

VL - 37

SP - 5550

EP - 5558

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 16

M1 - gkp558

ER -