Dataset Information

Chemical space guided discovery of antimicrobial bridged bicyclic peptides against Pseudomonas aeruginosa and its biofilms.

ABSTRACT: Herein we report the discovery of antimicrobial bridged bicyclic peptides (AMBPs) active against Pseudomonas aeruginosa, a highly problematic Gram negative bacterium in the hospital environment. Two of these AMBPs show strong biofilm inhibition and dispersal activity and enhance the activity of polymyxin, currently a last resort antibiotic against which resistance is emerging. To discover our AMBPs we used the concept of chemical space, which is well known in the area of small molecule drug discovery, to define a small number of test compounds for synthesis and experimental evaluation. Our chemical space was calculated using 2DP, a new topological shape and pharmacophore fingerprint for peptides. This method provides a general strategy to search for bioactive peptides with unusual topologies and expand the structural diversity of peptide-based drugs.

SUBMITTER: Di Bonaventura I

PROVIDER: S-EPMC5643981 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Chemical space guided discovery of antimicrobial bridged bicyclic peptides against <i>Pseudomonas aeruginosa</i> and its biofilms.

Di Bonaventura Ivan I Jin Xian X Visini Ricardo R Probst Daniel D Javor Sacha S Gan Bee-Ha BH Michaud Gaëlle G Natalello Antonino A Doglia Silvia Maria SM Köhler Thilo T van Delden Christian C Stocker Achim A Darbre Tamis T Reymond Jean-Louis JL

Chemical science 20170713 10

Herein we report the discovery of antimicrobial bridged bicyclic peptides (AMBPs) active against <i>Pseudomonas aeruginosa</i>, a highly problematic Gram negative bacterium in the hospital environment. Two of these AMBPs show strong biofilm inhibition and dispersal activity and enhance the activity of polymyxin, currently a last resort antibiotic against which resistance is emerging. To discover our AMBPs we used the concept of chemical space, which is well known in the area of small molecule dr ...[more]

PMID: 29147502

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Project description:The norbornadiene (NBD) molecule, C7H8, owes its fame to its remarkable photoswitching properties that are promising for molecular solar-thermal energy storage systems. Besides this photochemical interest, NBD is a rather unreactive species within astrophysical conditions and it should exhibit high photostability, properties that might also position this molecule as an important constituent of the interstellar medium (ISM)-especially in environments that are well shielded from short-wavelength radiation, such as dense molecular clouds. It is thus conceivable that, once formed, NBD can survive in dense molecular clouds and act as a carbon sink. Following the recent interstellar detections of large hydrocarbons, including several cyano-containing ones, in the dense molecular cloud TMC-1, it is thus logical to consider searching for NBD-which presents a shallow but non-zero permanent electric dipole moment (0.06 D)-as well as for its mono- and dicyano-substituted compounds, referred to as CN-NBD and DCN-NBD, respectively. The pure rotational spectra of NBD, CN-NBD, and DCN-NBD have been measured at 300 K in the 75-110 GHz range using a chirped-pulse Fourier-transform millimetre-wave spectrometer. Of the three species, only NBD was previously studied at high resolution in the microwave domain. From the present measurements, the derived spectroscopic constants enable prediction of the spectra of all three species at various rotational temperatures (up to 300 K) in the spectral range mapped at high resolution by current radio observatories. Unsuccessful searches for these molecules were conducted toward TMC-1 using the QUIJOTE survey, carried out at the Yebes telescope, allowing derivation of the upper limits to the column densities of 1.6 × 1014 cm-2, 4.9 × 1010 cm-2, and 2.9 × 1010 cm-2 for NBD, CN-NBD, and DCN-NBD, respectively. Using CN-NBD and cyano-indene as proxies for the corresponding bare hydrocarbons, this indicates that-if present in TMC-1-NBD would be at least four times less abundant than indene.

Dataset Information

Chemical space guided discovery of antimicrobial bridged bicyclic peptides against Pseudomonas aeruginosa and its biofilms.

Publications

Chemical space guided discovery of antimicrobial bridged bicyclic peptides against <i>Pseudomonas aeruginosa</i> and its biofilms.

Similar Datasets

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