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Interaction of α-Melanocortin and Its Pentapeptide Antisense LVKAT: Effects on Hepatoprotection in Male CBA Mice
St. Catherine’s Hospital, Bračak 8, 49210 Zabok, Croatia
Department of Pharmacology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Domagojeva 2, 10000 Zagreb, Croatia
Department of General and Inorganic Chemistry, Faculty of Pharmacy and Biochemistry, University of Zagreb, Ante Kovačića 1, 10000 Zagreb, Croatia
Ruđer Bošković Institute, Bijenička cesta 54, 10002 Zagreb, Croatia
* Author to whom correspondence should be addressed.
Received: 26 July 2011; in revised form: 23 August 2011 / Accepted: 23 August 2011 / Published: 26 August 2011
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 discontinuous 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.
Keywords: α-MSH; antisense; peptide; fluorescence; binding; hepatoprotection
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Houra, K.; Turčić, P.; Gabričević, M.; Weitner, T.; Konjevoda, P.; Štambuk, N. Interaction of α-Melanocortin and Its Pentapeptide Antisense LVKAT: Effects on Hepatoprotection in Male CBA Mice. Molecules 2011, 16, 7331-7343.
Houra K, Turčić P, Gabričević M, Weitner T, Konjevoda P, Štambuk N. Interaction of α-Melanocortin and Its Pentapeptide Antisense LVKAT: Effects on Hepatoprotection in Male CBA Mice. Molecules. 2011; 16(9):7331-7343.
Houra, Karlo; Turčić, Petra; Gabričević, Mario; Weitner, Tin; Konjevoda, Paško; Štambuk, Nikola. 2011. "Interaction of α-Melanocortin and Its Pentapeptide Antisense LVKAT: Effects on Hepatoprotection in Male CBA Mice." Molecules 16, no. 9: 7331-7343.