Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 1986 Apr;1(2):149-60.

DNA sequence selectivity of three biosynthetic analogues of the quinoxaline antibiotics

Affiliations
  • PMID: 3450291

DNA sequence selectivity of three biosynthetic analogues of the quinoxaline antibiotics

C M Low et al. Anticancer Drug Des. 1986 Apr.

Abstract

Mono- and bis-quinoline analogues of echinomycin, and a bis-3-amino-quinoxaline analogue of triostin A, have been prepared by directed biosynthesis and investigated for sequence selectivity in binding to DNA. Binding isotherms for bis-3-amino triostin A interacting with four natural and two synthetic DNA species have been determined by using solvent-partition analysis with radiolabelled antibiotic. They reveal a similar pattern of preferences to that seen with the parent compound: tighter binding occurs with the more guanine and cytosine (GC)-rich DNAs and in every case the association constant is increased two- to five-fold over the value recorded for triostin A. Deoxyribonuclease I footprinting patterns measured for the quinoline analogues of echinomycin differ from those observed with the parent antibiotic in that an additional strong site of protection occurs around the CpG sequence at position 35 in the tyrT fragment. Footprints for bis-3-amino triostin A reveal a substantially more selective pattern of cleavage inhibition than seen with the natural antibiotics: only two or three distinct binding sites are identified in tyrT DNA and four in pTyr2 DNA. Each is centred around one or more CpG steps, but many more CpG-containing sequences are unprotected. The analogue seems to prefer CpG steps flanked by at least one adenine and thymine (AT) pair, optimally ACGN. Enhancement of cutting at AT-rich sequences surrounding their binding sites is seen with all three of the new antibiotics. The results lend weight to the idea that novel sequence selectivity can be attained by making appropriate substitution on the chromophores of quinoxaline antibiotics.

PubMed Disclaimer

Publication types

LinkOut - more resources