title: Novel analogs of alloferon: Synthesis, conformational studies, pro-apoptotic and antiviral activity.
abstract: In this study, we report the structure-activity relationships of novel derivatives of the insect peptide alloferon (H-His-Gly-Val-Ser-Gly-His-Gly-Gln-His-Gly-Val-His-Gly-OH). The peptide structure was modified by exchanging His at position 9 or 12 for natural or non-natural amino acids. Biological properties of these peptides were determined in antiviral in vitro test against Human Herpes Virus 1 McIntrie strain (HHV-1MC) using a Vero cell line. The peptides were also evaluated for the pro-apoptotic action in vivo on hemocytes of the Tenebrio molitor beetle. Additionally, the structural properties of alloferon analogs were examined by the circular dichroism in water and methanol. It was found that most of the evaluated peptides can reduce the HHV-1 titer in Vero cells. [Ala(9)]-alloferon exhibits the strongest antiviral activity among the analyzed compounds. However, no cytotoxic activity against Vero cell line was observed for all the studied peptides. In vivo assays with hemocytes of T. molitor showed that [Lys(9)]-, [Phg(9)]-, [Lys(12)]-, and [Phe(12)]-alloferon exhibit a twofold increase in caspases activity in comparison with the native peptide. The CD conformational studies indicate that the investigated peptides seem to prefer the unordered conformation.
authors.affiliation: Faculty of Chemistry, University of Wrocław, 14 F. Joliot-Curie Str., 50-383 Wrocław, Poland. Electronic address: mariola.kuczer@chem.uni.wroc.pl.
authors.forename: Mariola
authors.initials: M
authors.lastname: Kuczer
authors.affiliation: Department of Animal Physiology and Development, Institute of Experimental Biology, Adam Mickiewicz University, 89 Umultowska Str., 61-614 Poznań, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Czarniewska
authors.affiliation: Department of Medical Microbiology, Medical University of Warsaw, 5 Chałubińskiego Str., 02-005 Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Majewska
authors.affiliation: Faculty of Chemistry, University of Wrocław, 14 F. Joliot-Curie Str., 50-383 Wrocław, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Różanowska
authors.affiliation: Department of Animal Physiology and Development, Institute of Experimental Biology, Adam Mickiewicz University, 89 Umultowska Str., 61-614 Poznań, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Rosiński
authors.affiliation: Faculty of Chemistry, University of Wrocław, 14 F. Joliot-Curie Str., 50-383 Wrocław, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Lisowski
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002522:Chlorocebus aethiops; D001517:Coleoptera; D004305:Dose-Response Relationship, Drug; D006434:Hemocytes / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014709:Vero Cells
chemical_list: C510535:Alloferon; D000998:Antiviral Agents; D010455:Peptides
keywords: Alloferon; Antiviral activity; Antiviral peptides; Apoptosis; Hemocytes; Insect peptide