Interaction of myo-inositol hexakisphosphate with biogenic and synthetic polyamines

Abstract

Within all the eukaryotic cells myo-inositol phosphates (InsPs) are an important group of biomolecules that are potentially related to signaling functions. The most abundant member of this family in nature is InsP₆ (phytate, L¹²⁻ in its fully deprotonated form). The complicated chemical behavior of this molecule demands a great effort to understand its function in the cell medium. In this work we follow our earlier studies on the interaction of InsP₆ with metal cations by inclusion of polyamines (both biogenic and synthetic) as potential agents to produce stable adducts. The stability constants of InsP₆–amine adducts and the relevant thermodynamic parameters ΔG°, ΔH°, and ΔS° were determined at 37.0 °C and 0.15 M ionic strength by means of potentiometric titrations and isothermal titration calorimetry (ITC). The biogenic amines studied were 1,4-diaminobutane (putrescine, put), 1,5-diaminopentane (cadaverine, cad), N-(3-aminopropyl)-1,4-diaminobutane (spermidine, spd), N,N′-bis(3-aminopropyl)-1,4-diaminobutane (spermine, spm), and 1-(4-aminobutyl)guanidine (agmatine, agm), while the synthetic models of longer polyamines were 1,19-dimethyl-1,4,7,10,13,16,19-heptaazanonadecane (Me₂hexaen), 1,22-dimethyl-1,4,7,10,13,16,19,22-octaazadocosane (Me₂heptaen), 1,25-dimethyl-1,4,7,10,13,16,19,22,25-nonaazapentacosane (Me₂octaen) and N,N′-bis(3-aminopropyl)-1,3-propanediamine (3,3,3-tet). With the aid of molecular modeling, we also studied the structural aspects of molecular recognition in operation. The final result is a balance between many parameters including charge of the species, flexibility of the amines, H-bonds in the adduct, and desolvation processes.