title: Interaction of α-melanocortin and its pentapeptide antisense LVKAT: effects on hepatoprotection in male CBA mice.
abstract: The genetic code defines nucleotide patterns that code for individual amino acids and their complementary, i.e., antisense, pairs. Peptides specified by the complementary mRNAs often bind to each other with a higher specificity and efficacy. Applications of this genetic code property in biomedicine are related to the modulation of peptide and hormone biological function, selective immunomodulation, modeling of continuous and linear epitopes, modeling of mimotopes, paratopes and antibody mimetics, peptide vaccine development, peptidomimetic and drug design. We have investigated sense-antisense peptide interactions and related modulation of the peptide function by modulating the effects of a-MSH on hepatoprotection with its antisense peptide LVKAT. First, transcription of complementary mRNA sequence of a-MSH in 3'→5' direction was used to design antisense peptide to the central motif that serves as a-MSH pharmacophore for melanocortin receptors. Second, tryptophan spectrofluorometric titration was applied to evaluate the binding of a-MSH and its central pharmacophore motif to the antisense peptide, and it was concluded that this procedure represents a simple and efficient method to evaluate sense-antisense peptide interaction in vitro. Third, we showed that antisense peptide LVKAT abolished potent hepatoprotective effects of a-MSH in vivo.
authors.affiliation: St. Catherine's Hospital, Zabok, Croatia.
authors.forename: Karlo
authors.initials: K
authors.lastname: Houra
authors.forename: Petra
authors.initials: P
authors.lastname: Turčić
authors.forename: Mario
authors.initials: M
authors.lastname: Gabričević
authors.forename: Tin
authors.initials: T
authors.lastname: Weitner
authors.forename: Paško
authors.initials: P
authors.lastname: Konjevoda
authors.forename: Nikola
authors.initials: N
authors.lastname: Stambuk
mesh_terms: D000082:Acetaminophen; D000410:Alanine Transaminase / Q000097:blood; D000595:Amino Acid Sequence; D000818:Animals; D016375:Antisense Elements (Genetics); D001219:Aspartate Aminotransferases; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000517:prevention & control; D019610:Cytoprotection / Q000187:drug effects*; D005815:Genetic Code; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009336:Necrosis / Q000139:chemically induced; D009842:Oligopeptides / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D011485:Protein Binding; D000521:alpha-MSH / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D016375:Antisense Elements (Genetics); C568716:LVKAT peptide; D009842:Oligopeptides; D000082:Acetaminophen; D000521:alpha-MSH; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase