Computational design of highly selective antimicrobial peptides

Journal of Chemical Information and Modeling
Davor JuretićAlessandro Tossi

Abstract

We have created a structure-selectivity database (AMPad) of frog-derived, helical antimicrobial peptides (AMPs), in which the selectivity was determined as a therapeutic index (TI), and then used the novel concept of sequence moments to study the lengthwise asymmetry of physicochemical peptide properties. We found that the cosine of the angle between two sequence moments obtained with different hydrophobicity scales, defined as the D-descriptor, identifies highly selective peptide antibiotics. We could then use this descriptor to predict TI changes after point mutations in known AMPs, and to aid the prediction of TI for de novo designed AMPs. In combination with an amino acid selectivity index, a motif regularity index and other statistical rules extracted from AMPad, the D-descriptor enabled construction of the AMP-Designer algorithm. A 23 residue, glycine-rich, peptide suggested by the algorithm was synthesized and the activity and selectivity tested. This peptide, adepantin 1, is less than 50% identical to any other AMP, has a potent antibacterial activity against the reference organism, E. coli, and has a significantly greater selectivity (TI > 200) than the best AMP present in the AMPad database (TI = 125).

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Citations

Jan 29, 2011·European Biophysics Journal : EBJ·Davor JuretićAlessandro Tossi
Oct 26, 2012·Journal of Chemical Information and Modeling·Nédia KamechDavor Juretić
Dec 17, 2011·Nature Reviews. Drug Discovery·Christopher D FjellGisbert Schneider
Jun 10, 2010·PloS One·E Besray UnalBurak Erman
Jul 9, 2011·PloS One·Carlos Polanco GonzálezGabriel del Rio
Jul 18, 2015·Pharmaceuticals·Biljana Mojsoska, Håvard Jenssen
Jun 5, 2012·Journal of Bioscience and Bioengineering·Wataru AokiMitsuyoshi Ueda
Jul 12, 2011·International Journal of Antimicrobial Agents·Raymond M DawsonChun-Qiang Liu
Sep 4, 2015·Journal of Chemical Information and Modeling·Mara KozićDavor Juretić
Mar 23, 2011·Journal of Peptide Science : an Official Publication of the European Peptide Society·Qing-Quan MaXing-Jun Feng
Mar 10, 2016·Journal of Chemical Information and Modeling·Alejandro Speck-PlancheM N D S Cordeiro
Feb 18, 2014·Biochimica Et Biophysica Acta·Juraj SimunićDavor Juretić
Jun 30, 2016·Journal of Peptide Science : an Official Publication of the European Peptide Society·Suhas RameshFernando Albericio
Apr 21, 2017·The Journal of Physical Chemistry. B·M-A SaniF Separovic
May 5, 2017·Bioinformatics·Alex T MüllerGisbert Schneider
Nov 28, 2013·Pharmaceuticals·Wataru Aoki, Mitsuyoshi Ueda
Jun 25, 2014·Antimicrobial Agents and Chemotherapy·Marco CantisaniStefania Galdiero
May 21, 2009·The Biochemical Journal·Nikolinka AntchevaAlessandro Tossi
Oct 21, 2011·Chemical Society Reviews·Søren L PedersenKnud J Jensen
Jul 18, 2019·Expert Opinion on Drug Discovery·Davor Juretić, Juraj Simunić
Nov 6, 2014·Expert Review of Anti-infective Therapy·Su-Jin KangBong-Jin Lee
Aug 6, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Davor JuretićFrançois-Xavier Pellay
Oct 1, 2020·Journal of Personalized Medicine·Vivian GarzónDaniel G Pinacho
Jul 4, 2020·Scientific Reports·Patrick Brendan Timmons, Chandralal M Hewage
Mar 15, 2019·BioData Mining·Sebastian Spänig, Dominik Heider
Jun 6, 2019·Pharmaceuticals·Boris VishnepolskyMalak Pirtskhalava
Dec 1, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Patrick Brendan Timmons, Chandralal M Hewage
Oct 7, 2021·Advanced Materials·Kenward JungCyrille Boyer
Nov 16, 2021·ACS Chemical Biology·Apurva PanjlaSandeep Verma

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