Rationally modified antimicrobial peptides from the N-terminal domain of human RNase 3 show exceptional serum stability

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  • dc.contributor.author Sandín, Daniel
  • dc.contributor.author Valle, Javier
  • dc.contributor.author Chaves-Arquero, Belén
  • dc.contributor.author Prats-Ejarque, Guillem
  • dc.contributor.author Larrosa, María Nieves
  • dc.contributor.author González-López, Juan José
  • dc.contributor.author Jiménez, María Ángeles
  • dc.contributor.author Boix, Ester
  • dc.contributor.author Andreu Martínez, David
  • dc.contributor.author Torrent Burgas, Marc
  • dc.date.accessioned 2022-01-25T07:29:51Z
  • dc.date.available 2022-01-25T07:29:51Z
  • dc.date.issued 2021
  • dc.description.abstract Multidrug resistance against conventional antibiotics poses an important threat to human health. In this context, antimicrobial peptides (AMPs) have been extensively studied for their antibacterial activity and promising results have been shown so far. However, AMPs tend to be rather vulnerable to protease degradation, which offsets their therapeutic appeal. Here, we demonstrate how replacing functional residues in the antimicrobial region of human RNase 3-also named eosinophil cationic protein-by non-natural amino acids increases stability in human serum. These changes were also shown to reduce the hemolytic effect of the peptides in general terms, whereas the antimicrobial activity was reasonably preserved. Digestion profiles enabled us to design new peptides with superior stability and lower toxicity that could become relevant candidates to reach clinical stages.
  • dc.description.sponsorship This work was supported by the Spanish Ministerio de Ciencia, Innovación y Universidades: SAF2015-72518-EXP, SAF2017-82158-R and RYC-2012-09999 to M.T.; CTQ2017-84371-P to M.A.J.; AGL2014-52395-C2; AGL2017-84097-C2-2-R to D.A. and PID2019-106123GB-I00 to E.B. Additional financial support from the European Society for Clinical Microbiology and Infectious Disease, ESCMID 2016, to M.T., the Secretaria d’Universitats i Recerca del Departament d’Empresa i Coneixement de la Generalitat de Catalunya, 2019 LLAV 00029 to M.T. and 2016 PROD 00060 to E.B. The “María de Maeztu” Program for Units of Excellence in R&D from the Spanish Ministry of Innovation and Competitiveness (MINECO) for work at Pompeu Fabra University (D.A.) is acknowledged. This work was supported, in part, by the European Regional Development Fund ‘A Way to Achieve Europe’ [Spanish Network for Research in Infectious Diseases (Grant No. RD16/0016/0003)]. D.S. and B.C.-A. are recipients of pre-doctoral FPI scholarships (PRE2018-083243 and BES-2015-073383, respectively) from the Spanish Ministerio de Ciencia, Innovación y Universidades.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Sandín D, Valle J, Chaves-Arquero B, Prats-Ejarque G, Larrosa MN, González-López JJ, Jiménez MÁ, Boix E, Andreu D, Torrent M. Rationally modified antimicrobial peptides from the N-terminal domain of human RNase 3 show exceptional serum stability. J Med Chem. 2021;64(15):11472-82. DOI: 10.1021/acs.jmedchem.1c00795
  • dc.identifier.doi http://dx.doi.org/10.1021/acs.jmedchem.1c00795
  • dc.identifier.issn 0022-2623
  • dc.identifier.uri http://hdl.handle.net/10230/52306
  • dc.language.iso eng
  • dc.publisher American Chemical Society (ACS)
  • dc.relation.ispartof J Med Chem. 2021;64(15):11472-82
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015-72518-EXP
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/SAF2017-82158-R
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/RYC-2012-09999
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/CTQ2017-84371-P
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/AGL2014-52395-C2
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/AGL2017-84097-C2-2-R
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-106123GB-I00
  • dc.rights © 2021 American Chemical Society. This work is licensed under a Creative Commons Attribution 4.0 International License
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri https://creativecommons.org/licenses/by/4.0/
  • dc.title Rationally modified antimicrobial peptides from the N-terminal domain of human RNase 3 show exceptional serum stability
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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