title: Synthesis and Evaluation of Biological Activity of Antimicrobial--Pro-Proliferative Peptide Conjugates.
abstract: Skin represents the largest organ of the human body and plays a crucial role in its protection from the negative impact of the outside environment, maintains its homeostasis, enables sensory interaction and thermoregulation. The traumatized skin tissue undergoes several phenotype switches due to progressive reoxygenation and release of cytokine and growth factors, that activate mechanisms of reparative processes. However, in case of wounds colonized with pathogenic microflora natural regenerative mechanisms become substantially impaired, that could lead to chronic inflammatory states with non-healing skin lesions. Herein, we present the initial results of our studies aimed at the design of bifunctional peptide-based compounds. The chemical approach, that was utilized in this work, was based on the conjugation of antimicrobial peptides with the peptides, that have potential pro-proliferative and/or cytoprotective activity towards human keratinocytes and fibroblasts, in order to obtain antimicrobials with reduced cytotoxicity or compounds that maintain both activities, i.e. inhibit bacterial or fungi growth and activate cell proliferation/migration in in vitro tests. As a result, we obtained a group of peptide conjugates that effectively inhibited the growth of selected bacterial and fungi strains and were able to stimulate proliferation and migration of keratinocytes and fibroblasts under their effective microbicidal concentrations.
authors.affiliation: Department of Biochemistry, Faculty of Chemistry, University of Gdansk, Gdansk, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Kosikowska
authors.affiliation: Department of Clinical Immunology and Transplantology, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Pikula
authors.affiliation: Department of Clinical Immunology and Transplantology, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Langa
authors.affiliation: Department of Clinical Immunology and Transplantology, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Trzonkowski
authors.affiliation: Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology UG-MUG, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Obuchowski
authors.affiliation: Department of Biochemistry, Faculty of Chemistry, University of Gdansk, Gdansk, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Lesner
mesh_terms: D000368:Aged; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001419:Bacteria / Q000254:growth & development*; D001833:Body Temperature Regulation / Q000187:drug effects; D002175:Candida / Q000254:growth & development*; D049109:Cell Proliferation / Q000187:drug effects*; D019610:Cytoprotection / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000382:microbiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000378:metabolism* / Q000382:microbiology
chemical_list: D023181:Antimicrobial Cationic Peptides