Biologically active peptides fragments derived from food proteins are inactive within the sequence of the precursor proteins but can be released by enzymatic proteolysis; they should be taken into account as potential modulators of various regulatory processes in the body. Opioid peptides are opioid receptors ligands with agonistic or antagonistic activities; they have been divided into two groups, so called 'typical' and 'atypical'. Opioid receptor are most abundant in the central nervous system, but have also been localized in many peripheral tissue of the mammalian organism, they are classified in µ, ?, ? and ? type which again can be divided into subtypes, i.e. ?1, ?2 receptors etc.. Opioid receptors and opioid peptides are distributed over the mammalian organism, indicating important functional significance. In fact, a variety of function has been proposed for these "opioidergic systems". For peptide neurotransmitter, transfer of their biological messages to the target cell via specific receptors requires at least two consecutive events: (1) binding of the neurotransmitter to its receptor and (2) transduction of the information from the complex into the cell. Since the structural, conformational, and dynamic properties opioid peptide and its receptor play a key role in both steps, their recognition and control are essential prerequisites to understanding the molecular basis in these systems. We have pursued this goal by examination of the conformational and dynamic properties of synthetic analogues carefully selected for their particular primary structure. Conformational change in a receptor upon binding a ligand (usually termed induced fit) could be the result of polar or hydrophobic interactions of the receptor with the ligand. We are interested to quantify the relative contributions of each of these interactions to the stability of the preferred structure that the peptide-ligand assume. In this work it has been observed tetra- and penta-peptides fragments of N-terminal protected ?-lactorphin (Tyr-Gly-Leu-Phe), ?-lactorfin (Tyr-Leu-Leu-Phe), gluten exorphins A4 (Gly-Tyr-Tyr-Pro), gluten exorphins C (Tyr-Pro-Ile-Ser-Leu), LVV-hemorphin-2 (Leu-Val-Val-Tyr-Pro). They have structures quite different from the endogenous and exogenous opioid peptides but are well known to be opioid receptor ligands. These products have been synthesized, purified, and then analyzed by NMR spectroscopy, employing both mono- and bi- dimensional homo- and hetero- nuclear correlation 1H-1H, 1H-13C techniques through which it is possible to obtain structural and conformational informations. The result obtained are compared and discussed. References -Fenude E., Roggio A.M., (1-8), XXII Congresso Nazionale della Società Chimica Italiana, 10-15 Settembre 2006 Firenze -Fenude E. Dedola S., Fais M., VII Convegno "Complex Systems: structure, properties, reactivity, and dynamics, Alghero, 13-15 Giugno 2005 -Fenude E., Villano R., SardiniaChem2008 Giornata di Studio Dedicata alla Chimica Organica delle Molecole Biologicamente Attive, 30 Maggio 2008 Sassari -Fanciulli G, Azara E, Wood TD, Dettori A, Delitala G, Marchetti M. J Chromatogr B Analyt Technol Biomed Life Sci. 2006 Apr 3; 833(2):204-9. Epub 2006 Feb 28
Study of Structural, Conformational and Dynamic Properties of Exorphin Fragments
Fenude Emma
2015
Abstract
Biologically active peptides fragments derived from food proteins are inactive within the sequence of the precursor proteins but can be released by enzymatic proteolysis; they should be taken into account as potential modulators of various regulatory processes in the body. Opioid peptides are opioid receptors ligands with agonistic or antagonistic activities; they have been divided into two groups, so called 'typical' and 'atypical'. Opioid receptor are most abundant in the central nervous system, but have also been localized in many peripheral tissue of the mammalian organism, they are classified in µ, ?, ? and ? type which again can be divided into subtypes, i.e. ?1, ?2 receptors etc.. Opioid receptors and opioid peptides are distributed over the mammalian organism, indicating important functional significance. In fact, a variety of function has been proposed for these "opioidergic systems". For peptide neurotransmitter, transfer of their biological messages to the target cell via specific receptors requires at least two consecutive events: (1) binding of the neurotransmitter to its receptor and (2) transduction of the information from the complex into the cell. Since the structural, conformational, and dynamic properties opioid peptide and its receptor play a key role in both steps, their recognition and control are essential prerequisites to understanding the molecular basis in these systems. We have pursued this goal by examination of the conformational and dynamic properties of synthetic analogues carefully selected for their particular primary structure. Conformational change in a receptor upon binding a ligand (usually termed induced fit) could be the result of polar or hydrophobic interactions of the receptor with the ligand. We are interested to quantify the relative contributions of each of these interactions to the stability of the preferred structure that the peptide-ligand assume. In this work it has been observed tetra- and penta-peptides fragments of N-terminal protected ?-lactorphin (Tyr-Gly-Leu-Phe), ?-lactorfin (Tyr-Leu-Leu-Phe), gluten exorphins A4 (Gly-Tyr-Tyr-Pro), gluten exorphins C (Tyr-Pro-Ile-Ser-Leu), LVV-hemorphin-2 (Leu-Val-Val-Tyr-Pro). They have structures quite different from the endogenous and exogenous opioid peptides but are well known to be opioid receptor ligands. These products have been synthesized, purified, and then analyzed by NMR spectroscopy, employing both mono- and bi- dimensional homo- and hetero- nuclear correlation 1H-1H, 1H-13C techniques through which it is possible to obtain structural and conformational informations. The result obtained are compared and discussed. References -Fenude E., Roggio A.M., (1-8), XXII Congresso Nazionale della Società Chimica Italiana, 10-15 Settembre 2006 Firenze -Fenude E. Dedola S., Fais M., VII Convegno "Complex Systems: structure, properties, reactivity, and dynamics, Alghero, 13-15 Giugno 2005 -Fenude E., Villano R., SardiniaChem2008 Giornata di Studio Dedicata alla Chimica Organica delle Molecole Biologicamente Attive, 30 Maggio 2008 Sassari -Fanciulli G, Azara E, Wood TD, Dettori A, Delitala G, Marchetti M. J Chromatogr B Analyt Technol Biomed Life Sci. 2006 Apr 3; 833(2):204-9. Epub 2006 Feb 28I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
