Transferring the purine 2-amino group from guanines to adenines in DNA changes the sequence-specific binding of antibiotics.

Abstract:

: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 inosine plus 2,6-diaminopurine (DAP). Irrespective of their mode of interaction with DNA, such GC-specific antibiotics as actinomycin, echinomycin, 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 of the '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-containing sites in natural DNA.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Bailly C,Waring MJ

doi

10.1093/nar/23.6.885

subject

Has Abstract

pub_date

1995-03-25 00:00:00

pages

885-92

issue

6

eissn

0305-1048

issn

1362-4962

pii

5b0002

journal_volume

23

pub_type

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