Nucleic Acids Research, 1995, Vol. 23, No. 6 885-892
© 1995
CHEMISTRY |
Transferring the purine 2-amino group from guanines to adenines in DNA changes the sequence-specific binding of antibiotics
Department of Pharmacology, University of Cambridge Tennis Court Road, Cambridge CB2 1QJ, UK
*To whom correspondence should be addressed
Received January 20, 1995. Revised February 9, 1995. Accepted February 9, 1995.
The proposition that the 2-amino group of guanine plays a critical role in determining how antibiotics recognise their binding sites in DNA has been tested by relocating it, using tyrT DNA derivative molecules substituted with inoslne plus 2,6-diamlnopurine (DAP). Irrespective of their mode of interaction with DNA, such GC-specific antibiotics as actinomycin, echino-mycin, mithramycin and chromomycin find new binding sites associated with DAP-containing sequences and are excluded from former canonical sites containing I·C base pairs. The converse is found to be the case for a group of normally AT-selective ligands which bind in the minor groove of the helix, such as netropsin: their preferred sites become shifted to IC-rich clusters. Thus the binding sites of all these antibiotics strictly follow the placement of the purine 2-amino group, which accordingly must serve as both a positive and negative effector. The footprinting profile ofthe ‘threading’ intercalator nogalamycin is potentiated In DAP plus inosine-substituted DNA but otherwise remains much the same as seen with natural DNA. The interaction of echinomycin with sites containing the TpDAP step in doubly substituted DNA appears much stronger than its interaction with CpG-contalnlng sites in natural DNA.
+Present address: Institut de Recherches sur le Cancer, INSERM Unité 124, Place de Verdun, 59045 Lille, France
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Lindemose, P. E. Nielsen, and N. E. Mollegaard Dissecting direct and indirect readout of cAMP receptor protein DNA binding using an inosine and 2,6-diaminopurine in vitro selection system Nucleic Acids Res., August 1, 2008; 36(14): 4797 - 4807. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Bailly, P. Colson, C. Houssier, E. Rodrigues-Pereira, M. Prudhomme, and M. J. Waring Recognition of Specific Sequences in DNA by a Topoisomerase I Inhibitor Derived from the Antitumor Drug Rebeccamycin Mol. Pharmacol., January 1, 1998; 53(1): 77 - 87. [Abstract] [Full Text]
|
|
|
|
 |
|
 C. Bailly, D. Payet, A. A. Travers, and M. J. Waring PCR-based development of DNA substrates containing modified bases: An efficient system for investigating the role of the exocyclic groups in chemical and structural recognition by minor groove binding drugs and proteins PNAS, November 26, 1996; 93(24): 13623 - 13628. [Abstract] [Full Text] [PDF]
|
|