title: Enhanced antimicrobial activity of a peptide derived from human lysozyme by arylation of its tryptophan residues.
abstract: Antimicrobial peptides are valuable agents to fight antibiotic resistance. These amphipatic species display positively charged and hydrophobic amino acids. Here, we enhance the local hydrophobicity of a model peptide derived from human lysozyme (107RKWVWWRNR115) by arylation of its tryptophan (Trp) residues, which renders a positive effect on Staphylococcus aureus and Staphylococcus epidermidis growth inhibition. This site-selective modification was accessed by solid-phase peptide synthesis using the non-proteinogenic amino acid 2-aryltryptophan, generated by direct C-H activation from protected Trp. The modification brought about a relevant increase in growth inhibition: S. aureus was fully inhibited by arylation of Trp 112 and by only 10% by arylation of Trp 109 or 111, respect to the non-arylated peptide. On the other hand, S. epidermidis was fully inhibited by the three arylated peptides and the parent peptide. The minimum inhibitory concentration was significantly reduced for S. aureus depending on the arylation site.
authors.affiliation: Cathedra of Biotechnology, School of Pharmacy and Biochemistry, UBA, and NANOBIOTEC, UBA-CONICET, Junín 956, (1113), Buenos Aires, Argentina.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: González
authors.affiliation: Department of Organic Chemistry, School of Chemistry, University of Barcelona, Martí i Franquès 1-11, 08028, Barcelona, Spain.|Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac 10, 08028, Barcelona, Spain.|CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Barcelona Science Park, Baldiri Reixac 10, 08028, Barcelona, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: Mendive-Tapia
authors.affiliation: Cathedra of Biotechnology, School of Pharmacy and Biochemistry, UBA, and NANOBIOTEC, UBA-CONICET, Junín 956, (1113), Buenos Aires, Argentina.
authors.forename: María B
authors.initials: MB
authors.lastname: Pastrian
authors.affiliation: Department of Organic Chemistry, School of Chemistry, University of Barcelona, Martí i Franquès 1-11, 08028, Barcelona, Spain.|Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac 10, 08028, Barcelona, Spain.|CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Barcelona Science Park, Baldiri Reixac 10, 08028, Barcelona, Spain.|School of Chemistry and Physics, University of KwaZulu-Natal, Westville Campus, University Road, Westville, 4001, Durban, South Africa.
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
authors.affiliation: Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona, Barcelona Science Park, Baldiri Reixac 10-12, 08028, Barcelona, Spain.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Lavilla
authors.affiliation: Cathedra of Biotechnology, School of Pharmacy and Biochemistry, UBA, and NANOBIOTEC, UBA-CONICET, Junín 956, (1113), Buenos Aires, Argentina.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Cascone
authors.affiliation: Cathedra of Biotechnology, School of Pharmacy and Biochemistry, UBA, and NANOBIOTEC, UBA-CONICET, Junín 956, (1113), Buenos Aires, Argentina.
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Iannucci
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009113:Muramidase / Q000737:chemistry* / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects; D013212:Staphylococcus epidermidis / Q000187:drug effects; D014364:Tryptophan / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D010446:Peptide Fragments; D014364:Tryptophan; D009113:Muramidase
keywords: antimicrobial activity; arylation; human lysozyme; peptide; tryptophan