Abstract
| Language | English |
|---|---|
| Pages | 795-822 |
| Number of pages | 27 |
| Journal | Helvetica Chimica Acta |
| Volume | 92 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2009 |
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Keywords
- Lexitropsin
- DNA
- minor groove binder
- NMR spectroscopy
- molecular dynamics calculation
- peptide DNA complexes
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Comparison of DNA complex formation behaviour for two closely related lexitropsin analogues. / Parkinson, J.A.; Khalaf, A.I.; Anthony, N.G.; Mackay, S.P.; Suckling, C.J.; Waigh, R.D.
In: Helvetica Chimica Acta, Vol. 92, No. 5, 2009, p. 795-822.Research output: Contribution to journal › Article
TY - JOUR
T1 - Comparison of DNA complex formation behaviour for two closely related lexitropsin analogues
AU - Parkinson, J.A.
AU - Khalaf, A.I.
AU - Anthony, N.G.
AU - Mackay, S.P.
AU - Suckling, C.J.
AU - Waigh, R.D.
PY - 2009
Y1 - 2009
N2 - Two closely related lexitropsin analogues that differ only in the form of the headgroup functionality (CHO (for 1) vs. Ac (for 2)) have been studied in their DNA-binding capacity for the sequence d(GCATATATGC) using 1H-NMR spectroscopy. DNA-Complex formation for the CHO derivative was apparent from the observation of new NMR signals on titration of DNA with ligand. Detailed investigation and assignment of the data for a ligand/DNA-duplex ratio of 2 : 1 clearly delineated the structure as one associated with the minor groove class of DNA complexes. The structure of the complex was determined on the basis of the acquired NMR data. Features characteristic of typical 2 : 1 minor-groove complexes were apparent. In a similar experimental approach, the Ac analogue ligand-DNA binding response was investigated. Despite the close similarity in chemical structure to the CHO case, the Ac analogue was found to produce NMR data of a much poorer quality. This was attributed to more rapid on/off chemical exchange equilibrium between ligand and DNA. From close analysis and comparison of the NMR data for the Ac and CHO headgroup ligand-DNA complexes, it was possible to ascertain that the same type of complex formed in each case but with different relative binding constants. Consideration of the nature and form of these complexes has been made with reference to a previously determined structure from our laboratory for the related lexitropsin analogue thiazotropsin A.
AB - Two closely related lexitropsin analogues that differ only in the form of the headgroup functionality (CHO (for 1) vs. Ac (for 2)) have been studied in their DNA-binding capacity for the sequence d(GCATATATGC) using 1H-NMR spectroscopy. DNA-Complex formation for the CHO derivative was apparent from the observation of new NMR signals on titration of DNA with ligand. Detailed investigation and assignment of the data for a ligand/DNA-duplex ratio of 2 : 1 clearly delineated the structure as one associated with the minor groove class of DNA complexes. The structure of the complex was determined on the basis of the acquired NMR data. Features characteristic of typical 2 : 1 minor-groove complexes were apparent. In a similar experimental approach, the Ac analogue ligand-DNA binding response was investigated. Despite the close similarity in chemical structure to the CHO case, the Ac analogue was found to produce NMR data of a much poorer quality. This was attributed to more rapid on/off chemical exchange equilibrium between ligand and DNA. From close analysis and comparison of the NMR data for the Ac and CHO headgroup ligand-DNA complexes, it was possible to ascertain that the same type of complex formed in each case but with different relative binding constants. Consideration of the nature and form of these complexes has been made with reference to a previously determined structure from our laboratory for the related lexitropsin analogue thiazotropsin A.
KW - Lexitropsin
KW - DNA
KW - minor groove binder
KW - NMR spectroscopy
KW - molecular dynamics calculation
KW - peptide DNA complexes
UR - http://dx.doi.org/10.1002/hlca.200800390
U2 - 10.1002/hlca.200800390
DO - 10.1002/hlca.200800390
M3 - Article
VL - 92
SP - 795
EP - 822
JO - Helvetica Chimica Acta
T2 - Helvetica Chimica Acta
JF - Helvetica Chimica Acta
SN - 0018-019X
IS - 5
ER -