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.
References
Apr 15, 1994·The Biochemical Journal·E Pérez-PayáS E Blondelle
May 25, 1999·FEBS Letters·E J HelmerhorstA V Nieuw Amerongen
Sep 19, 2001·The Journal of Biological Chemistry·H R IbrahimA Pellegrini
Mar 1, 1997·Journal of Applied Microbiology·A PellegriniR von Fellenberg
Jun 8, 2006·Journal of the American Chemical Society·Gijsbert M GrotenbregMark Overhand
Feb 16, 2008·Nature Protocols·Irith WiegandRobert E W Hancock
Dec 17, 2009·Chemistry : a European Journal·Javier Ruiz-RodríguezRodolfo Lavilla
Jun 29, 2010·Journal of Peptide Science : an Official Publication of the European Peptide Society·Rodrigo GonzálezNancy B Iannucci
Jul 20, 2013·The Journal of Organic Chemistry·Sara PreciadoRodolfo Lavilla
Aug 29, 2013·Biopolymers·N B IannucciJ M Delfino
Jul 26, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Juanjuan TanYuxin Chen
Aug 12, 2014·Langmuir : the ACS Journal of Surfaces and Colloids·Christopher Aisenbrey, Burkhard Bechinger
Dec 2, 2014·Nature Reviews. Microbiology·Jessica M A BlairLaura J V Piddock
May 23, 2015·Nature Communications·Lorena Mendive-TapiaRodolfo Lavilla
Jun 24, 2015·ACS Medicinal Chemistry Letters·Peter G M WutsAke P Elhammer
Sep 10, 2015·Organic & Biomolecular Chemistry·Steven M WalesStephen G Pyne
Citations
Jun 30, 2016·Journal of Peptide Science : an Official Publication of the European Peptide Society·Suhas RameshFernando Albericio
Apr 25, 2018·Journal of Medicinal Food·Wilman Carrillo, Mercedes Ramos
Apr 27, 2018·Journal of Medicinal Food·Wilman CarrilloGrace Vásquez
Aug 10, 2019·Critical Reviews in Clinical Laboratory Sciences·Adriana Barreto-SantamaríaHernando Curtidor
Apr 1, 2020·Current Topics in Medicinal Chemistry·Andrea BossoElio Pizzo
Jan 7, 2019·Journal of Molecular Biology·Marcelo D T TorresCesar de la Fuente-Nunez
Jun 3, 2021·Biomolecules·Xiaomin GuoJunqiu Xie
Aug 11, 2017·Journal of Medicinal Chemistry·Shimaa A H Abdel MonaimBeatriz G de la Torre