title: Modulating short tryptophan- and arginine-rich peptides activity by substitution with histidine.
abstract: High antimicrobial efficacy of short tryptophan-and arginine-rich peptides makes them good candidates in the fight against pathogens. Substitution of tryptophan and arginine by histidine could be used to modulate the peptides efficacy by optimizing their structures.
  
  
  
  The peptide (RRWWRWWRR), reported to showed good antimicrobial efficacy, was used as template, seven new analogs being designed substituting tryptophan or arginine with histidine. The peptides' efficacy was tested against E. coli, B. subtilis and S. aureus. The cytotoxicity and hemolytic effect were evaluated and the therapeutic index was inferred for each peptide. Atomic force microscopy and molecular simulation were used to analyze the effects of peptides on bacterial membrane.
  
  
  
  The substitution of tryptophan by histidine proved to strongly modulate the antimicrobial activity, mainly by changing the peptide-to-membrane binding energy. The substitution of arginine has low effect on the antimicrobial efficacy. The presence of histidine residue reduced the cytotoxic and hemolytic activity of the peptides in some cases maintaining the same efficacy against bacteria. The peptides' antimicrobial activity was correlated to the 3D-hydrophobic moment and to a simple structure-based packing parameter.
  
  
  
  The results show that some of these peptides have the potential to become good candidates to fight against bacteria. The substitution by histidine proved to fine tune the therapeutic index allowing the optimization of the peptide structure mainly by changing its binding energy and 3D-hydrophobic moment.
  
  
  
  The short tryptophan reach peptides therapeutic index can be maximized using the histidine substitution to optimize their structure.
authors.affiliation: Department of Life and Environmental Physics, Horia Hulubei National Institute for Physics and Nuclear Engineering, Reactorului 30, PO Box MG-6, Măgurele 077125, Romania.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Bacalum
authors.affiliation: Molecular and Biomolecular Physics Department, National Institute for Research and Development of Isotopic and Molecular Technologies, 65-103 Donath Street, 400293 Cluj-Napoca, Romania.
authors.forename: Lorant
authors.initials: L
authors.lastname: Janosi
authors.affiliation: Multipurpose Irradiation Facility Center, Horia Hulubei National Institute for Physics and Nuclear Engineering, Reactorului 30, PO Box MG-6, Măgurele 077125, Romania.
authors.forename: Florina
authors.initials: F
authors.lastname: Zorila
authors.affiliation: Babeş-Bolyai University, Supramolecular Organic and Organometallic Chemistry Center (SOOMCC), Cluj-Napoca, 11 Arany Janos Street, 400028 Cluj-Napoca, Romania.
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Tepes
authors.affiliation: Applied Nuclear Physics Department, Horia Hulubei National Institute for Physics and Nuclear Engineering, Reactorului 30, PO Box MG-6, Măgurele 077125, Romania.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ionescu
authors.affiliation: Babeş-Bolyai University, Supramolecular Organic and Organometallic Chemistry Center (SOOMCC), Cluj-Napoca, 11 Arany Janos Street, 400028 Cluj-Napoca, Romania.
authors.forename: Elena
authors.initials: E
authors.lastname: Bogdan
authors.affiliation: Babeş-Bolyai University, Supramolecular Organic and Organometallic Chemistry Center (SOOMCC), Cluj-Napoca, 11 Arany Janos Street, 400028 Cluj-Napoca, Romania.
authors.forename: Niculina
authors.initials: N
authors.lastname: Hadade
authors.affiliation: Applied Nuclear Physics Department, Horia Hulubei National Institute for Physics and Nuclear Engineering, Reactorului 30, PO Box MG-6, Măgurele 077125, Romania.
authors.forename: Liviu
authors.initials: L
authors.lastname: Craciun
authors.affiliation: Babeş-Bolyai University, Supramolecular Organic and Organometallic Chemistry Center (SOOMCC), Cluj-Napoca, 11 Arany Janos Street, 400028 Cluj-Napoca, Romania.
authors.forename: Ion
authors.initials: I
authors.lastname: Grosu
authors.affiliation: Molecular and Biomolecular Physics Department, National Institute for Research and Development of Isotopic and Molecular Technologies, 65-103 Donath Street, 400293 Cluj-Napoca, Romania. Electronic address: ioan.turcu@itim-cj.ro.
authors.forename: Ioan
authors.initials: I
authors.lastname: Turcu
authors.affiliation: Department of Life and Environmental Physics, Horia Hulubei National Institute for Physics and Nuclear Engineering, Reactorului 30, PO Box MG-6, Măgurele 077125, Romania. Electronic address: mradu@nipne.ro.
authors.forename: Mihai
authors.initials: M
authors.lastname: Radu
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D001120:Arginine; D002462:Cell Membrane / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006639:Histidine; D006801:Humans; D008958:Models, Molecular; D010455:Peptides / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship; D014364:Tryptophan
chemical_list: D000890:Anti-Infective Agents; D010455:Peptides; D006639:Histidine; D014364:Tryptophan; D001120:Arginine
keywords: Antimicrobial peptides; Arginine; Cytotoxicity; Molecular simulations; Therapeutic index; Tryptophan