Hx, a Novel Fluorescent, Minor Groove and Sequence Specific Recognition Element: Design, Synthesis, and DNA Binding Properties ofp-Anisylbenzimidazole-imidazole/pyrrole-Containing Polyamides

Biochemistry ◽  
2011 ◽  
Vol 50 (15) ◽  
pp. 3127-3136 ◽  
Author(s):  
Sameer Chavda ◽  
Yang Liu ◽  
Balaji Babu ◽  
Ryan Davis ◽  
Alan Sielaff ◽  
...  
Keyword(s):  
Dna Binding ◽  
Minor Groove ◽  
Binding Properties ◽  
Design Synthesis ◽  
Recognition Element ◽  
Specific Recognition ◽  
Dna Binding Properties

Rational Design, Synthesis, and DNA Binding Properties of Novel Sequence-Selective Peptidyl Congeners of Ametantrone

ChemMedChem ◽  
2010 ◽  
Vol 5 (7) ◽  
pp. 1080-1091 ◽  
Author(s):  
Alessandra Gianoncelli ◽  
Serena Basili ◽  
Matteo Scalabrin ◽  
Alice Sosic ◽  
Stefano Moro ◽  
...  
Keyword(s):  
Dna Binding ◽  
Rational Design ◽  
Binding Properties ◽  
Design Synthesis ◽  
Dna Binding Properties

Design, Synthesis, and DNA Binding Properties of Photoisomerizable Azobenzene−Distamycin Conjugates: An Experimental and Computational Study

2008 ◽  
Vol 19 (12) ◽  
pp. 2332-2345 ◽  
Author(s):  
Sumana Ghosh ◽  
Dandamudi Usharani ◽  
Ananya Paul ◽  
Susmita De ◽  
Eluvathingal D. Jemmis ◽  
...  
Keyword(s):  
Dna Binding ◽  
Computational Study ◽  
Binding Properties ◽  
Design Synthesis ◽  
Dna Binding Properties

scholarly journals 1052. Characterisation of the DNA binding properties of ridinilazole, a selective antibiotic currently in phase III trials for the treatment of Clostridioides difficile

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S617-S617
Author(s):  
Clive Mason ◽  
Tim Avis ◽  
Chris Coward ◽  
David Powell ◽  
Esther Duperchy ◽  
...  
Keyword(s):  
Dna Binding ◽  
Confocal Microscopy ◽  
Mechanism Of Action ◽  
Tight Binding ◽  
Minor Groove ◽  
Phase Iii ◽  
Sequence Specificity ◽  
Binding Properties ◽  
Clostridioides Difficile ◽  
Dna Binding Properties

Abstract Background Clostridioides difficile infection (CDI) is recognised by the CDC as an “urgent threat” in the USA, responsible for nearly 13,000 deaths, and carries an economic burden ranging from &5.4 to &6.3 billion per year. In a phase II study, ridinilazole was shown to be effective at treating CDI and decreasing subsequent recurrence compared to vancomycin. However, the precise mechanism of action of ridinilazole has yet to be fully elucidated. We now present data that reveals ridinilazole clearly co-localises with DNA in C. difficile and binds with high affinity to the minor groove of DNA. These interactions are predicted to have consequences on cellular functions within C. difficile. Methods High resolution confocal microscopy was used to track the intracellular localisation of ridinilazole in C. difficile. Fluorescence intensity was used to characterise the DNA binding properties of ridinilazole; sequence specificity was demonstrated with AT- or GC-rich DNA polymers, and tight binding was shown using short double-stranded oligonucleotides. Hanging drop vapour diffusion enabled co-crystallisation and subsequent structural determination of DNA-bound ridinilazole. Results Confocal microscopy revealed clear co-localisation of ridinilazole to the DNA within C. difficile. Ridinilazole demonstrated a dose-dependent increase in fluorescence in response to increasing concentration of target DNA. Fluorescence binding studies revealed that ridinilazole shows a preference towards AT-rich DNA sequences. Tight binding characteristics were demonstrated by ridinilazole in complex with short double-stranded oligonucleotides, returning dissociation constants (Kd) of 20 – 50 nM. Crystallisation enabled co-structures of ridinilazole bound to the minor groove of double-stranded DNA oligonucleotides to be solved. Conclusion Ridinilazole demonstrates tight binding with sequence specificity within the minor groove of DNA and co-localises with DNA in C. difficle. Further analysis is ongoing to fully understand this novel mechanism of action, the downstream consequences of these interactions and how they contribute to the bactericidal activity of ridinilazole. Disclosures Clive Mason, PhD, Summit Therapeutics (Employee, Shareholder) Tim Avis, n/a, Summit therapeutics (Shareholder) Chris Coward, PhD, Summit Therapeutics (Employee, Scientific Research Study Investigator, Shareholder) David Powell, PhD, Summit Therapeutics (Employee) Kevin W. Garey, Pharm.D., M.S., FASHP, Summit Therapeutics (Research Grant or Support)

Design, synthesis and DNA binding properties of orthogonally positioned diamino containing polyamide f-IPI

2011 ◽  
Vol 404 (3) ◽  
pp. 848-852 ◽  
Author(s):  
Balaji Babu ◽  
Yang Liu ◽  
Adam Plaunt ◽  
Camille Riddering ◽  
Ross Ogilvie ◽  
...  
Keyword(s):  
Dna Binding ◽  
Binding Properties ◽  
Design Synthesis ◽  
Dna Binding Properties
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