2. Academic Validation
  3. Rationally Modified Antimicrobial Peptides from the N-Terminal Domain of Human RNase 3 Show Exceptional Serum Stability

Rationally Modified Antimicrobial Peptides from the N-Terminal Domain of Human RNase 3 Show Exceptional Serum Stability

  • J Med Chem. 2021 Aug 12;64(15):11472-11482. doi: 10.1021/acs.jmedchem.1c00795.
Daniel Sandín 1,  Javier Valle 2,  Belén Chaves-Arquero 3,  Guillem Prats-Ejarque 1,  María Nieves Larrosa 4 5,  Juan José González-López 4 5,  María Ángeles Jiménez 3,  Ester Boix 1,  David Andreu 2,  Marc Torrent 1
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Cerdanyola del Vallès 08193, Spain.
  • 2 Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona Biomedical Research Park, Barcelona 08003, Spain.
  • 3 Departamento de Química-Física Biológica, Instituto de Química Física Rocasolano (IQFR-CSIC), Serrano 119, Madrid 28006, Spain.
  • 4 Servei de Microbiologia, Hospital Universitari Vall d'Hebron, Barcelona 08035, Spain.
  • 5 Departament de Genètica i Microbiologia, Universitat Autònoma de Barcelona, Cerdanyola del Vallès 08193, Spain.
PMID: 34342438 DOI: 10.1021/acs.jmedchem.1c00795
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.

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