1,101 results match your criteria distamycin

In search of drugs to alleviate suppression of the host's innate immune responses against SARS-CoV-2 using a molecular modeling approach.

In Silico Pharmacol 2021 4;9(1):26. Epub 2021 Apr 4.

Department of Zoology, Dhemaji College, Dhemaji, Assam 787057 India.

Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), Middle East Respiratory Syndrome coronavirus (MERS-CoV) and the novel SARS-CoV-2 evade the host innate immunity, and subsequently the adaptive immune response, employing one protease called Papain-like protease (PLpro). The PLpro and the 3CL main protease are responsible for the cleavage of the polyproteins encoded by the + sense RNA genome of the virus to produce several non-structured proteins (NSPs). However, the PLpro also performs deubiquitination and deISGylation of host proteins and signaling molecules, and thus antagonize the host innate immune response, since ubiquitination and ISGylation are critical processes which invoke host's antiviral immune responses. Read More

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An atomistic investigation on the interaction of distamycin A and its derivative with the telomeric G-Quadruplex as anticancer agents by molecular dynamics simulation.

Arch Biochem Biophys 2021 04 16;701:108797. Epub 2021 Feb 16.

Department of Cell and Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran. Electronic address:

Human telomerase that activates within cancer cells has a telomeric sequence at the 3' end. Each factor that stabilizes the G-quadruplex in guanine-rich telomeric sequences can inhibit the regular telomerase activity. Therefore, the telomeric G-quadruplex is known as a promising target in cancer treatment. Read More

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Natural and Synthetic Oligoarylamides: Privileged Structures for Medical Applications.

Chemistry 2021 May 4;27(26):7321-7339. Epub 2021 Mar 4.

Institut für Organische Chemie und Biomolekulares Wirkstoffzentrum, (BMWZ), Leibniz Universität Hannover, Schneiderberg 1B, 30167, Hannover, Germany.

The term "privileged structure" refers to a single molecular substructure or scaffold that can serve as a starting point for high-affinity ligands for more than one receptor type. In this report, a hitherto overlooked group of privileged substructures is addressed, namely aromatic oligoamides, for which there are natural models in the form of cystobactamids, albicidin, distamycin A, netropsin, and others. The aromatic and heteroaromatic core, together with a flexible selection of substituents, form conformationally well-defined scaffolds capable of specifically binding to conformationally well-defined regions of biomacromolecules such as helices in proteins or DNA often by acting as helices mimics themselves. Read More

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Specific stabilization of promoter G-Quadruplex DNA by 2,6-disubstituted amidoanthracene-9,10-dione based dimeric distamycin analogues and their selective cancer cell cytotoxicity.

Eur J Med Chem 2020 Jun 16;195:112202. Epub 2020 Mar 16.

Department of Organic Chemistry, Indian Institute of Science, Bangalore, 560012, India; School of Applied & Interdisciplinary Sciences, Indian Association for the Cultivation of Science, Kolkata, 700032, India. Electronic address:

We have designed and synthesized anthraquinone containing compounds which have oligopyrrole side chains of varying lengths. These compounds stabilized the G-quadruplex DNA formed in the promoter regions of c-MYC oncogenes selectively over the duplex DNA. These observations were recorded using UV-vis spectroscopic titrations, fluorescence measurements and circular dichroism (CD) spectral titrations. Read More

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Revised Structure of Anthelvencin A and Characterization of the Anthelvencin Biosynthetic Gene Cluster.

ACS Chem Biol 2020 04 23;15(4):945-951. Epub 2020 Mar 23.

Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay, 91198, Gif-sur-Yvette cedex, France.

Anthelvencins A and B are pyrrolamide metabolites produced by ATCC 14583 and 14585. Isolated in 1965, they were reported to exhibit anthelmintic and moderate antibacterial activities. In this study, we revise the structure of anthelvencin A and identify a third anthelvencin metabolite, bearing two -methylated pyrrole groups, which we named anthelvencin C. Read More

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Novel distamycin analogues that block the cell cycle of African trypanosomes with high selectivity and potency.

Eur J Med Chem 2020 Mar 8;189:112043. Epub 2020 Jan 8.

Group Redox Biology of Trypanosomes, Institut Pasteur de Montevideo, Montevideo, Uruguay. Electronic address:

Polyamides-based compounds related to the Streptomycetal distamycin and netropsin are potent cytostatic molecules that bind to AT-rich regions of the minor groove of the DNA, hence interfering with DNA replication and transcription. Recently, derivatives belonging to this scaffold have been reported to halt the proliferation of deadly African trypanosomes by different and unrelated mechanisms. Here we describe the synthesis and preliminary characterization of the anti-trypanosomal mode of action of new potent and selective distamycin analogues. Read More

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Correcting electrostatic artifacts due to net-charge changes in the calculation of ligand binding free energies.

J Comput Chem 2020 04 12;41(10):986-999. Epub 2020 Jan 12.

Institute of Molecular Modeling and Simulation, University of Natural Resources and Life Sciences, Vienna, Austria.

Alchemically derived free energies are artifacted when the perturbed moiety has a nonzero net charge. The source of the artifacts lies in the effective treatment of the electrostatic interactions within and between the perturbed atoms and remaining (partial) charges in the simulated system. To treat the electrostatic interactions effectively, lattice-summation (LS) methods or cutoff schemes in combination with a reaction-field contribution are usually employed. Read More

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Three putative DNA replication/repair elements encoding genes confer self-resistance to distamycin in Streptomyces netropsis.

Acta Biochim Biophys Sin (Shanghai) 2020 Jan;52(1):91-96

Institute of TCM and Natural Products, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education) and Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China.

Distamycin (DST) is a well-characterized DNA minor groove binder with antivirus activity and antitumor potency. Two separate gene clusters (a 28-kb cluster and a 7-kb cluster) have recently been identified to coordinately encode the biosynthetic machinery of DST in Streptomyces netropsis. Here we report a gene cassette, which is linked to the aforementioned smaller dst gene cluster and plays an important role in the self-resistance to DST in S. Read More

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January 2020

Carbocyclic Analogues of Distamycin and Netropsin.

Mini Rev Med Chem 2019 ;19(2):98-113

Department of Organic Chemistry, Medical University, Bialystok 15-222, Mickiewicza Street 2c, Poland.

The DNA as the depository of genetic information is a natural target for chemotherapy. A lot of anticancer and antimicrobial agents derive their biological activity from their selective interaction with DNA in the minor groove and from their ability to interfere with biological processes such as enzyme catalysis, replication and transcription. The discovery of the details of minor groove binding drugs, such as netropsin and distamycin A, oligoamides built of 4-amino-1-methylpyrrole-2-carboxylic acid residues, allowed to develop various DNA sequence-reading molecules, named lexitropsins, capable of interacting with DNA precisely, strongly and with a high specificity, and at the same time exhibiting significant cytotoxic potential. Read More

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January 2019

Thermodynamics and site stoichiometry of DNA binding by a large antiviral hairpin polyamide.

Biochimie 2019 Feb 24;157:149-157. Epub 2018 Nov 24.

Department of Chemistry & Biochemistry, University of Missouri St. Louis, St. Louis, MO, 63121, USA. Electronic address:

PA1 (dIm-PyPyβPyPyPy-γ-PyPyβPyPyPyPyβ-Ta) is a large (14-ring) hairpin polyamide that was designed to recognize the DNA sequence 5'-WGW-3', where W is either A or T. As is common among the smaller 6-8-ring hairpin polyamides (PAs), it binds its target recognition sequence with low nM affinity. However, in addition to its large size, it is distinct from these more extensively characterized PAs in its high tolerance for mismatches and antiviral properties. Read More

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February 2019

Thermodynamic Study of Interactions of Distamycin A with Chromatin in Rat Liver Nuclei in the Presence of Polyamines.

Biochemistry (Mosc) 2018 Oct;83(10):1231-1244

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119991, Russia.

We studied the thermodynamics of melting of isolated rat liver nuclei with different degrees of chromatin condensation determined by the concentration of polyamines (PA) and the solution ionic strength, as well as the effect of the antibiotic distamycin A (DM) on melting. Differential scanning calorimetry (DSC) profiles of nuclear preparations contained three peaks that reflected melting of three main chromatin domains. The number of peaks did not depend on the degree of condensation; however, nuclei with more condensed chromatin had a higher total enthalpy. Read More

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October 2018

Cell penetrating thiazole peptides inhibit c-MYC expression via site-specific targeting of c-MYC G-quadruplex.

Nucleic Acids Res 2018 06;46(11):5355-5365

Department of Organic Chemistry, Indian Association for the Cultivation of Science, Kolkata 700032, India.

The structural differences among different G-quadruplexes provide an opportunity for site-specific targeting of a particular G-quadruplex structure. However, majority of G-quadruplex ligands described thus far show little selectivity among different G-quadruplexes. In this work, we delineate the design and synthesis of a crescent-shaped thiazole peptide that preferentially stabilizes c-MYC quadruplex over other promoter G-quadruplexes and inhibits c-MYC oncogene expression. Read More

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Enhanced Expression of FRA16B using AT-Rich DNA Binding Chemicals in a Woman with Secondary Amenorrhoea.

J Clin Diagn Res 2017 Jun 1;11(6):QD01-QD03. Epub 2017 Jun 1.

Professor and Head (Retd.), Department of of Genetics, Dr. ALM Postgraduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, Tamil Nadu, India.

Fragile sites represent regions of chromatin that fail to compact during mitosis. Based on the prevalence and pattern of inheritance they are classified as rare fragile sites or common fragile sites. Rare fragile sites either occur spontaneously or can be induced by certain AT-specific binding chemicals namely distamycin, Hoechst 33258, Berenil and others. Read More

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Targeting DNA Minor Groove by Hybrid Molecules as Anticancer Agents.

Curr Med Chem 2017 ;24(26):2887-2907

Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037. India.

Agents which can recognize and bind specific sequences of DNA offer selective therapy through the modulation of specific transcription factors or genes. Recently, there has been renewed interest in the field of anticancer minor groove binders. This may be attributed to the fact that many compounds of this class have demonstrated significant antitumor activity against a wide variety of cancers in recent clinical trials. Read More

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September 2017

An evaluation of Minor Groove Binders as anti-fungal and anti-mycobacterial therapeutics.

Eur J Med Chem 2017 Aug 17;136:561-572. Epub 2017 May 17.

WestCHEM Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, United Kingdom.

This study details the synthesis and biological evaluation of a collection of 19 structurally related Minor Groove Binders (MGBs), derived from the natural product distamycin, which were designed to probe antifungal and antimycobacterial activity. From this initial set, we report several MGBs that are worth more detailed investigation and optimisation. MGB-4, MGB-317 and MGB-325 have promising MICs of 2, 4 and 0. Read More

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DNA Minor Groove Binders-Inspired by Nature.

Acta Chim Slov 2016 12;63(4):689-704

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. Read More

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December 2016

Differential scanning calorimetric study of antibiotic distamycin A binding with chromatin within isolated rat liver nuclei.

Pharm Biol 2017 Dec;55(1):687-690

a A.N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University , Moscow , Russia.

Context: Natural oligopeptide antibiotic distamycin A (Dst) biosynthesized by Streptomyces distallicus is traditionally used in medical practice as an anti-inflammatory and antitumour drug.

Objective: Dst was investigated for its effect on the structural components of native chromatin directly within isolated rat liver nuclei in the presence of physiologically significant cations (magnesium or spermine and spermidine).

Materials And Methods: Differential scanning calorimetry (DSC) was used to study the Dst action at molar ratio Dst/DNA = 0. Read More

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December 2017

In vitro activity and mode of action of distamycin analogues against African trypanosomes.

Eur J Med Chem 2017 Jan 2;126:776-788. Epub 2016 Dec 2.

Laboratorio de Química Farmacéutica, Departamento de Química Orgánica, Facultad de Química, Universidad de la República, Montevideo, Uruguay. Electronic address:

Distamycin, a natural polyamide containing three heterocycle rings with a polar end, has inspired several groups to prepare synthetic analogues, which proved to have anti-trypanosomal and anti-tumoral activity. We describe the synthesis of bi and tri thiazoles amides that harbor different substitutions at their ends and the evaluation of their anti-Trypanosoma brucei activity. The most active compound 10b showed better biological activity (EC 310 nM and selectivity index 16) than the control drug nifurtimox (EC 15 μM and selectivity index 10). Read More

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January 2017

An evaluation of Minor Groove Binders as anti-lung cancer therapeutics.

Bioorg Med Chem Lett 2016 08 16;26(15):3478-86. Epub 2016 Jun 16.

WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, United Kingdom.

A series of 47 structurally diverse MGBs, derived from the natural product distamycin, was evaluated for anti-lung cancer activity by screening against the melanoma cancer cell line B16-F10. Five compounds have been found to possess significant activity, more so than a standard therapy, Gemcitabine. Moreover, one compound has been found to have an activity around 70-fold that of Gemcitabine and has a favourable selectivity index of greater than 125. Read More

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[Interaction of Dystamycin Dimeric Analog with Poly(dA) x poly(dT), Poly[d(A-T)] x poly[d(A-T)] and Duplex O23 at Origin of Replication of the Herpes Simplex Virus].

Biofizika 2016 Mar-Apr;61(2):270-6

The binding of distamycin dimeric analog (Pt-bis-Dst) to poly[d(A-T)] x poly[d(A-T)1, poly(dA) x poly(dT) and duplex O23 with the sequence 5'-GCCAATATATATATATTATTAGG-3' which is present at the origin of replication of herpes simplex virus OriS is investigated with the use of UV and CD spectroscopy. The distinction of the synthetic polyamide from a natural antibiotic lies in the fact that in the synthetic polyamide there are two distamycin moieties bound via a glycine cis-diamino platinum group. It was shown that the binding of Pt-bis-Dst to poly[d(A-T)] x poly[d(A-T)] and poly(dA) x poly(dT) reaches saturation if one molecule of the ligand occurs at approximately every 8 bp. Read More

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New Fe(iii) and Co(ii) salen complexes with pendant distamycins: selective targeting of cancer cells by DNA damage and mitochondrial pathways.

Dalton Trans 2016 May;45(22):9345-53

Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India and Indian Association for the Cultivation of Science, Kolkata, West Bengal 700 032, India.

Minor groove binding distamycin like moieties were conjugated with core salens and the corresponding Fe(iii) and Co(ii) complexes were synthesized. Herein, we have shown efficient DNA minor groove binding specificities along with excellent DNA cleavage capacities with metallosalen conjugates. The metal complexes showed toxicity toward various cancer cells over normal cells with high specificity. Read More

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An evaluation of Minor Groove Binders as anti-Trypanosoma brucei brucei therapeutics.

Eur J Med Chem 2016 Jun 29;116:116-125. Epub 2016 Mar 29.

WestCHEM Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, United Kingdom.

A series of 32 structurally diverse MGBs, derived from the natural product distamycin, was evaluated for activity against Trypanosoma brucei brucei. Four compounds have been found to possess significant activity, in the nanomolar range, and represent hits for further optimisation towards novel treatments for Human and Animal African Trypanosomiases. Moreover, SAR indicates that the head group linking moiety is a significant modulator of biological activity. Read More

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Acta Pol Pharm 2016 Jan-Feb;73(1):47-53

The evaluation of a new group of distamycin analogues 1-6 as potential minor groove binders for the treatment of cancer were investigated. The activity of the new compounds against several restriction enzymes was examined. The studied compounds did not block GC-rich sequences regions of DNA but inhibited catalytic action of endonucleases in AA, AT, TT and AG restriction sites. Read More

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Kinetic characterization of small DNA-binding molecules interacting with a DNA strand on a quartz crystal microbalance.

Anal Biochem 2016 Jan 25;492:34-42. Epub 2015 Sep 25.

Department of Biomolecular Engineering, Tokyo Institute of Technology, 4259, Nagatsuda, Midori-ku, Yokohama, Japan.

Quantitative studies of the binding of various DNA-binding antibiotics with dsDNA are useful for drug design, not only for effective antibiotics, but also for antitumor drugs. We studied the binding kinetics, association and dissociation rate constants, and association constants (kon, koff, and Ka, respectively) of intercalators and groove binders, including various antibiotics, to double-stranded DNA (dA30·dT30 and dG30·dC30) immobilized on a highly sensitive 27 MHz quartz-crystal microbalance (QCM) in aqueous solution. Although a simple ethidium bromide intercalator bound to both dA30·dT30 and dG30·dC30, antibiotics that are side-binding intercalators, such as daunomycin, aclacinomycin A, and actinomycin D, with sugar or peptide moieties on the intercalator parts selectively bound to dG30·dC30 with high Ka and small koff values. Read More

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January 2016

Liposomes as a potential ocular delivery system of distamycin A.

Int J Pharm 2015 Aug 13;492(1-2):120-6. Epub 2015 Jul 13.

Department of Pharmacy, University of Pisa, Pisa, Italy.

Liposomes containing Distamycin A (DA) may be clinically useful in the treatment of ocular HSV infections, especially in acyclovir-resistant HSV keratitis. This study evaluated the in vitro and in vivo performance of a topical controlled release liposomal formulation containing DA (DA-Lipo) aimed at reducing the toxicity of the encapsulated active agent and improving drug uptake by ocular tissues. The bioavailability of DA in the tear fluid and the DA uptake into the cornea were increased after instillation of DA-Lipo in rabbits, reaching the DA corneal concentration corresponding to IC50 values against HSV without any sign of transcorneal permeation of drug. Read More

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AzaHx, a novel fluorescent, DNA minor groove and G·C recognition element: Synthesis and DNA binding properties of a p-anisyl-4-aza-benzimidazole-pyrrole-imidazole (azaHx-PI) polyamide.

Bioorg Med Chem Lett 2015 Sep 19;25(17):3681-5. Epub 2015 Jun 19.

Cancer Research UK Drug-DNA Interactions Research Group, UCL Cancer Institute, London WC1E 6BT, UK.

The design, synthesis, and DNA binding properties of azaHx-PI or p-anisyl-4-aza-benzimidazole-pyrrole-imidazole (5) are described. AzaHx, 2-(p-anisyl)-4-aza-benzimidazole-5-carboxamide, is a novel, fluorescent DNA recognition element, derived from Hoechst 33258 to recognize G·C base pairs. Supported by theoretical data, the results from DNase I footprinting, CD, ΔT(M), and SPR studies provided evidence that an azaHx/IP pairing, formed from antiparallel stacking of two azaHx-PI molecules in a side-by-side manner in the minor groove, selectively recognized a C-G doublet. Read More

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September 2015

Synthesis, anti-mycobacterial activity and DNA sequence-selectivity of a library of biaryl-motifs containing polyamides.

Bioorg Med Chem 2015 Jul 8;23(13):3705-11. Epub 2015 Apr 8.

Mycobacteria Research Laboratory, Department of Biological Sciences, The Institute of Structural and Molecular Biology, Birkbeck, University of London, London WC1E 7HX, UK.

The alarming rise of extensively drug-resistant tuberculosis (XDR-TB) strains, compel the development of new molecules with novel modes of action to control this world health emergency. Distamycin analogues containing N-terminal biaryl-motifs 2(1-5)(1-7) were synthesised using a solution-phase approach and evaluated for their anti-mycobacterial activity and DNA-sequence selectivity. Thiophene dimer motif-containing polyamide 2(2,6) exhibited 10-fold higher inhibitory activity against Mycobacterium tuberculosis compared to distamycin and library member 2(5,7) showed high binding affinity for the 5'-ACATAT-3' sequence. Read More

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Minor-Groove Binding Agents: Rational Design of Carboxamide Bond Isosteres.

Curr Top Med Chem 2015 ;15(14):1359-71

Department of Chemistry, National Sun Yat Sen University, Kaohsiung, Taiwan.

Distamycin and netropsin analogues have been designed for targeting specific sequences in DNA. Numerous reviews have been centered on the replacement of N-methylpyrrole with heteroaromatic rings in order to induce better fitting to improve the binding efficiency and the introduction of additional interactions for recognition of GC base pairs at the minor groove of DNA. Most of these designed analogs retained the use of carboxamide-bond for interconnecting the heteroaromatic rings. Read More

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Extraction of histone H1 and decondensation of nuclear chromatin with various Mg-dependent organization levels under treatment with polyglutamic acid and distamycin.

Biochemistry (Mosc) 2015 Mar;80(3):356-65

Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, Moscow, 119991, Russia.

Chromatin in rat liver nuclei under conditions of low ionic strength (20-25 mM) and [Mg2+] from 2 to 5 mM has a condensed structure (100-200 nm globules) and gives the same CD signal (320-340 nm) at interaction with the antibiotic distamycin A (DM). Reducing [Mg2+] to 1 mM leads to chromatin decondensation to 30 nm structures and increases the CD signal. Poly-L-glutamic acid (PG) at weight ratio PG/DNA = 6 and in the presence of 5 mM Mg2+ extracts only about 1/8 of nuclear histone H1, preserving a condensed chromatin structure. Read More

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Probing the interaction of distamycin A with S100β: the "unexpected" ability of S100β to bind to DNA-binding ligands.

J Mol Recognit 2015 Jun 19;28(6):376-84. Epub 2015 Feb 19.

Giotto Biotech, Via Madonna del Piano 6, Sesto Fiorentino, Florence, 50019, Italy.

DNA-minor-groove-binding ligands are potent antineoplastic molecules. The antibiotic distamycin A is the prototype of one class of these DNA-interfering molecules that have been largely used in vitro. The affinity of distamycin A for DNA is well known, and the structural details of the complexes with some B-DNA and G-quadruplex-forming DNA sequences have been already elucidated. Read More

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