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Article

NMR Study of the Secondary Structure and Biopharmaceutical Formulation of an Active Branched Antimicrobial Peptide

1
Department of Medical Biotechnology, University of Siena, via Aldo Moro 2, 53100 Siena, Italy
2
Zambon S.p.a, Via della Chimica, 9. 36100 Vicenza, Italy
3
Magnetic Resonance Center (CERM), University of Florence, via Luigi Sacconi 6, 50019 Sesto Fiorentino (Firenze), Italy
4
Red Glead Discovery AB, Medicon Village, 223 81 Lund, Sweden
5
SetLance srl, via Aldo Moro 2, 53100 Siena, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Hirokazu Tamamura
Molecules 2019, 24(23), 4290; https://doi.org/10.3390/molecules24234290
Received: 15 October 2019 / Revised: 11 November 2019 / Accepted: 20 November 2019 / Published: 25 November 2019
(This article belongs to the Special Issue Peptide-Lead Drug Discovery)
The synthetic antimicrobial peptide SET-M33 is being developed as a possible new antibacterial candidate for the treatment of multi-drug resistant bacteria. SET-M33 is a branched peptide featuring higher resistance and bioavailability than its linear analogues. SET-M33 shows antimicrobial activity against different species of multi-resistant Gram-negative bacteria, including clinically isolated strains of Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumanii and Escherichia coli. The secondary structure of this 40 amino acid peptide was investigated by NMR to fully characterize the product in the framework of preclinical studies. The possible presence of helixes or β-sheets in the structure had to be explored to predict the behavior of the branched peptide in solution, with a view to designing a formulation for parenteral administration. Since the final formulation of SET-M33 will be strictly defined in terms of counter-ions and additives, we also report the studies on a new salt form, SET-M33 chloride, that retains its activity against Gram-negative bacteria and gains in solubility, with a possible improvement in the pharmacokinetic profile. The opportunity of using a chloride counter-ion is very convenient from a process development point of view and did not increase the toxicity of the antimicrobial drug. View Full-Text
Keywords: antimicrobial peptides; branched peptides; NMR structure; counter-ion antimicrobial peptides; branched peptides; NMR structure; counter-ion
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MDPI and ACS Style

Castiglia, F.; Zevolini, F.; Riolo, G.; Brunetti, J.; De Lazzari, A.; Moretto, A.; Manetto, G.; Fragai, M.; Algotsson, J.; Evenäs, J.; Bracci, L.; Pini, A.; Falciani, C. NMR Study of the Secondary Structure and Biopharmaceutical Formulation of an Active Branched Antimicrobial Peptide. Molecules 2019, 24, 4290. https://doi.org/10.3390/molecules24234290

AMA Style

Castiglia F, Zevolini F, Riolo G, Brunetti J, De Lazzari A, Moretto A, Manetto G, Fragai M, Algotsson J, Evenäs J, Bracci L, Pini A, Falciani C. NMR Study of the Secondary Structure and Biopharmaceutical Formulation of an Active Branched Antimicrobial Peptide. Molecules. 2019; 24(23):4290. https://doi.org/10.3390/molecules24234290

Chicago/Turabian Style

Castiglia, Francesca, Fabrizia Zevolini, Giulia Riolo, Jlenia Brunetti, Alessandra De Lazzari, Alberto Moretto, Giulia Manetto, Marco Fragai, Jenny Algotsson, Johan Evenäs, Luisa Bracci, Alessandro Pini, and Chiara Falciani. 2019. "NMR Study of the Secondary Structure and Biopharmaceutical Formulation of an Active Branched Antimicrobial Peptide" Molecules 24, no. 23: 4290. https://doi.org/10.3390/molecules24234290

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