Lipidic Membranes Are Potential “Catalysts” in the Ligand Activity of the Multifunctional Pentapeptide Neokyotorphin

Abstract

Neokyotorphin (NKT) is a multifunctional pentapeptide that is involved in biological functions as diverse as analgesia, antihibernatic regulation and proliferation stimulus of tumour cells. The interaction of neokyotorphin with cell membranes is potentially important to all these multiple biological processes since receptor-mediated processes are thought to be involved in neokyotorphin action. Sargent and Schwyzer proposed in their "membrane catalysis" model that ligands interact with membrane lipids in order to adopt the necessary conformation for cell receptors. We have used fluorescence techniques to study the depth, orientation and extent of incorporation of NKT with model membrane systems (lipidic vesicles). The roles of lipid charge, membrane phase and sterol presence were investigated. The phenolic ring of tyrosine is located in a shallow position in membranes. The extent of partition is less in gel crystalline membranes than in liquid crystalline membranes. Addition of cholesterol causes a reorientation of the tyrosine ring at the interface of lipidic bilayers. Lipidic membranes meet all the conditions required for acting as potential "catalysts" in the ligand activity of the multifunctional pentapeptide NKT, because they modulate the exposure and orientation of the phenolic ring, which is most likely involved in docking to receptors.