TY - JOUR
T1 - Multiple DNA binding modes of anthracene-9-carbonyl-N1-spermine
AU - Rodger, Alison
AU - Taylor, Steven
AU - Adlam, Gareth
AU - Blagbrough, Ian S.
AU - Haworth, Ian S.
PY - 1995/6
Y1 - 1995/6
N2 - The poly(dAdT)2 complex of anthracene-9-carbonyl-N1-spermine, a spermine derivative terminally substituted with an anthracene moiety, has been studied using fluorescence, linear dichroism, circular dichroism, normal absorption spectroscopy (as a function of temperature) and computer modelling. For comparison, some data are also provided for the same ligand with poly(dGdC)2 and calf thymus DNA. Following detailed fluorescence and CD spectroscopic studies, we propose that anthracene-9-carbonyl-N1-spermine intercalates in at least two different binding orientations with poly(dAdT)2. Based on computer simulation data, we deduce that the ligand can intercalate from both the minor groove and the major groove. In contrast, intercalation with poly(dGdC)2 probably occurs only from the major groove. At high ligand concentrations, the CD spectra suggest anthracene-anthracene interactions, whilst the LD data point towards a groove-bound anthracene. Again from computer simulations, we propose binding modes consistent with these observations. Other data from the LD spectra suggest a sequential nature to the binding of the ligand to calf thymus DNA, with GC-rich sites being occupied first. At low ligand concentrations, anthracene-9-carbonyl-N1-spermine is able to stabilize poly(dAdT)2 against thermal decomposition, but not as effectively as spermine. The reverse is found to be true with calf thymus DNA. Both the anthracene-9-carbonyl-N1-spermine and spermine complexes of poly(dAdT)2 show pre-melt transitions in their melting curves. The anthracene-9-carbonyl-N1-spermine complex with poly(dAdT)2 also shows a post-melt transition.
AB - The poly(dAdT)2 complex of anthracene-9-carbonyl-N1-spermine, a spermine derivative terminally substituted with an anthracene moiety, has been studied using fluorescence, linear dichroism, circular dichroism, normal absorption spectroscopy (as a function of temperature) and computer modelling. For comparison, some data are also provided for the same ligand with poly(dGdC)2 and calf thymus DNA. Following detailed fluorescence and CD spectroscopic studies, we propose that anthracene-9-carbonyl-N1-spermine intercalates in at least two different binding orientations with poly(dAdT)2. Based on computer simulation data, we deduce that the ligand can intercalate from both the minor groove and the major groove. In contrast, intercalation with poly(dGdC)2 probably occurs only from the major groove. At high ligand concentrations, the CD spectra suggest anthracene-anthracene interactions, whilst the LD data point towards a groove-bound anthracene. Again from computer simulations, we propose binding modes consistent with these observations. Other data from the LD spectra suggest a sequential nature to the binding of the ligand to calf thymus DNA, with GC-rich sites being occupied first. At low ligand concentrations, anthracene-9-carbonyl-N1-spermine is able to stabilize poly(dAdT)2 against thermal decomposition, but not as effectively as spermine. The reverse is found to be true with calf thymus DNA. Both the anthracene-9-carbonyl-N1-spermine and spermine complexes of poly(dAdT)2 show pre-melt transitions in their melting curves. The anthracene-9-carbonyl-N1-spermine complex with poly(dAdT)2 also shows a post-melt transition.
UR - http://www.scopus.com/inward/record.url?scp=0029030498&partnerID=8YFLogxK
U2 - 10.1016/0968-0896(95)00086-V
DO - 10.1016/0968-0896(95)00086-V
M3 - Article
C2 - 7582962
AN - SCOPUS:0029030498
SN - 0968-0896
VL - 3
SP - 861
EP - 872
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 6
ER -