Structural characterization of agmatine at physiological conditions

Structural Chemistry - Tập 17 - Trang 163-175 - 2006
Antonio Toninello1, Valentina Battaglia1, Mauro Salvi1, Rita Calheiros2, M. Paula M. Marques2,3
1Dipartimento di Chimica Biologica, Università degli Studi di Padova, Padova, Italia
2Unidade de Química-Física Molecular, Universidade de Coimbra, Coimbra, Portugal
3Departamento de Bioquímica, Faculdade de Ciências e Tecnologia, Universidade de Coimbra, Apartado, Portugal

Tóm tắt

The present work aims at determining the structure–activity relationships (SAR’s) which rule the biological function of agmatine (4-(aminobutyl)guanidinium, AGM), a biogenic amine produced by decarboxylation of arginine. Its structural preferences, both as an isolated molecule and in aqueous solution (namely at physiological conditions) were ascertained, by vibrational (Raman) spectroscopy coupled to theoretical (density functional) calculations. An evaluation of mitochondrial functions (membrane potential (ΔΨ), mitochondrial swelling, and cytochrome c release) in rat liver mitochondria (RLM) was also carried out. The results thus obtained, coupled to the conformational analysis performed for the distinct polyamine protonation states, allowed to individualize the agmatine structures which interact with the mitochondrial site responsible for its transport and for the protection against mitochondrial permeability transition (MPT) induction, as well as to gain information on the specific mechanisms involved.

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