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, L(12-) 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.

Synthesis, solid-state characterization and solution studies of new phytate compounds with Cu(ii) and 1,10-phenanthroline: progress in the structural elucidation of phytate coordinating ability

“…Previous protonation constants of InsP 6 determined by means of potentiometric and calorimetric titrations at 37.0 °C in 0.15 M Me 4 NCl were included in the Hyperquad calculations. 10 The Cu(II)-InsP 6 data were taken from our previous report under the same experimental conditions. 19 H + -phen and Cu(II)-phen interactions determined in this work are in line with the previously known values.…”

“…Other amines, previously studied, show similar behaviors. 10,19,48 Assuming that protonation is governed by the different basicities of the interacting species, the complex species should be better formulated as [( phen)(H n L)] (12−n)− (for n up to 6) or [(Hphen)(H n-1 L)] (12−n)− (for n higher than 6). Nevertheless, we cannot exclude that both complexes, with the same general stoichiometry but different proton distribution, might coexist in solution, in particular for interacting species of similar basicity.…”

“…7 These are highly charged and soluble species that exhibit a strong interaction with any cation present in the same medium. We and other groups have studied and quantified this interaction in depth by several techniques, [7][8][9][10][11] resulting in a large set of formation constants of species containing H x L (12−x)− and cations. This includes simple ions with different charges (Na + , K + , Li + , Mg 2+ , Ca 2+ , Mn 2+ , Fe 2+ , Fe 3+ , Co 2+ , Ni 2+ , Cu 2+ , Zn 2+ , Cd 2+ , etc.)…”

“…In this case, the interaction is a balance between many parameters including the charge of the species, the flexibility of amines, inter-and intramolecular H-bonds, and desolvation processes. 10 Structural information on the interaction occurring in these systems, in particular when parts of the molecule directly par-ticipate in such interactions with cationic species, is of utmost importance. The knowledge of the phosphate groups responsible for the high formation constants, and of possible selectivity patterns, could be used to predict the interaction with other inositol phosphates having a different number and disposition of phosphate groups.…”

An isothermal titration calorimetry study of phytate binding to lysozyme

“…It has been used successfully to characterise a diverse range of binding interactions [17], including how the b-propeller phytase hydrolyses insoluble calcium phytate salts and prevents phytate from binding to metal ions [18]. More recently, ITC has been used to determine how phytate could interact with amines in the cellular medium to gain a greater understanding of its function within cells [19]. However, it has not been used to measure the binding energetics between positively charged proteins and phytate.…”