DNA binding of a short lexitropsin.
Footprinting, capillary electrophoresis, molecular modelling and NMR studies have been used to examine the binding of a short polyamide to DNA. This molecule, which contains an isopropyl-substituted thiazole in place of one of the N-methylpyrroles, is selective for the sequence 5'-ACTAGT-3' to which it binds with high affinity. Two molecules bind side-by-side in the minor groove, but their binding is staggered so that the molecule reads six base pairs, unlike the related natural products, which tend to bind to four-base-pair sequences. The result suggests that high affinity and selectivity may be gained without resort to very large molecules, which may be difficult to deliver to the site of action.
Anthony
Nahoum G
NG
Department of Physiology and Pharmacology, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO9 3TU, UK.
Fox
Keith R
KR
Johnston
Blair F
BF
Khalaf
Abedawn I
AI
Mackay
Simon P
SP
McGroarty
Iain S
IS
Parkinson
John A
JA
Skellern
Graham G
GG
Suckling
Colin J
CJ
Waigh
Roger D
RD
D001665:Binding Sites; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D009429:Netropsin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding
D004268:DNA-Binding Proteins; C053654:lexitropsin; D009429:Netropsin; D004247:DNA