Preferred Binding Sites for [N-MeCys3,N-MeCys7]TANDEM Determined Using a Universal Footprinting Substrate

Lavesa, M; Fox, Keith R.

doi:10.1006/abio.2001.5124

Cited by 33 publications

(39 citation statements)

References 18 publications

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“…Footprinting studies have shown that 5 -ATAT is the binding site with highest affinity for this compound. 85 The lowest affinity site was 5 -TTAA, while 5 -CTAG was amongst the highest affinity sites. Free energy simulations have shown that when faced with identical hydrogen bonding opportunities with the minor groove, these compounds intercalate at sites with the best stacking properties.…”

Section: Biological Activity Of the Triostinsmentioning

confidence: 99%

Bisintercalator natural products with potential therapeutic applications: isolation, structure determination, synthetic and biological studies

et al. 2007

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Echinomycin is the prototypical bisintercalator, a molecule that binds to DNA by inserting two planar chromophores between the base-pairs of duplex DNA, placing its cyclic depsipeptide backbone in the minor groove. As such, it has been the focus of an extensive number of investigations into its biological activity, nucleic acid binding and, to some extent, its structure-activity relationships. However, echinomycin is also the parent member of an extended family of natural products that interact with DNA by a similar mechanism of bisintercalation. The structural variety in these compounds leads to changes in sequence selectivity and and biological activity, particularly as anti-tumour and anti-viral agents. One of the more recently identified marine natural products that is moving close to clinical development is thiocoraline, and it therefore seems timely to review the various bisintercalator natural products.

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Section: Biological Activity Of the Triostinsmentioning

confidence: 99%

Bisintercalator natural products with potential therapeutic applications: isolation, structure determination, synthetic and biological studies

et al. 2007

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“…The first approach [6] manually produced a DNA segment of length 166 containing all 136 tetranucleotide sequences, while at the same time minimising the occurrence of oligopurine/oligopyrimidine tracts and long blocks of AT or GC base pairs. The second approach [5] used random computer searches to generate DNA segments containing all possible 2-, 3-, 4-, 5-, and 7-mer targets.…”

Section: Introduction and Statements Of Resultsmentioning

confidence: 99%

A fast algorithm for the construction of universal footprinting templates in DNA

2005

Self Cite

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Abstract. We introduce and give a complete description of a new graph to be used for DNA sequencing questions. This graph has the advantage over the classical de Bruijn graph that it fully accounts for the double stranded nature of DNA, rather than dealing with single strands. Technically, our graph may be thought of as the quotient of the de Bruijn graph under the natural involution of sending a DNA strand to its complementary strand. However, this involution has fixed points, and this complicates the structure of the quotient graph which we have therefore modified herein.As an application and motivating example, we give an efficient algorithm for constructing universal footprinting templates for n-mers. This problem may be formulated as the task of finding a shortest possible segment of DNA which contains every possible sequence of base pairs of some fixed length n. Previous work by Kwan et al has attacked this problem from a numerical point of view and generated minimal length universal footprinting templates for n = 2, 3, 5, 7, together with unsubstantiated candidates for the case n = 4. We show that their candidates for n = 4 are indeed minimal length universal footprinting templates.

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“…4 shows the results of deoxyribonuclease I and hydroxyl radical footprinting experiments with these compounds on DNA fragments MS1 and MS2. 25,49 These footprinting substrates contain all the 136 possible tetranucleotide sequences: MS1 and MS2 contain the same sequence, which was cloned in opposite orientations, allowing good resolution of target sites at both ends of the fragment. The authors expected that Thiazotropsin B would possess a binding site that is longer than four base pairs [probably (A/T)CGCG(A/T)].…”

Section: Mgbs Containing Isopropylthiazole and N-methylimidazolementioning

confidence: 99%

DNA Minor Groove Binders-Inspired by Nature

Khalaf¹,

Al-kadhimi²,

Ali³

2016

ACSi

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The synthesis and biological activity of a variety of analogues to the naturally occurring antibacterial and antifungal Distamycin A were explored by a number of authors. These compounds were subject to a large array of assays. Some of these compounds showed high activity against a range of Gram-positive, Gram-negative bacteria as well as fungi. To explore the anti-parasitic activity of this class of compounds, specific modifications had to be made. A number of these compounds proved to be active against Trypanosoma brucei. The binding of a number of these compounds to short sequences of DNA were also examined using footprinting assays as well as NMR spectroscopy. Computer modelling was employed on selected compounds to understand the way these compounds bind to specific DNA sequences. A large number of variations were made to the standard structure of Distamycin. These changes involved the replacement of the pyrrole moieties as well as the head and tail groups with a number of heterocyclic compounds. Some of these minor groove binders (MGBs) were also investigated for their capability for the treatment of cancer and in particular lung cancer.

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Preferred Binding Sites for [N-MeCys3,N-MeCys7]TANDEM Determined Using a Universal Footprinting Substrate

Cited by 33 publications

References 18 publications

Bisintercalator natural products with potential therapeutic applications: isolation, structure determination, synthetic and biological studies

Bisintercalator natural products with potential therapeutic applications: isolation, structure determination, synthetic and biological studies

A fast algorithm for the construction of universal footprinting templates in DNA

DNA Minor Groove Binders-Inspired by Nature

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