Binding of polyamines

The weak binding of polyamines (Table 1) to sigma receptors suggests that polyamines may be the biological modulators of sigma receptors [8] ... 

A correlation of enhanced synthesis of polyamines with rapid growth or cell proliferation has been observed 21. From a physiological point of view, polyamines are implicated as regulators of cell proliferative activity 22). It is well known that polyamines, as protonated polycations, can bind with nucleotide and nucleic acid anions 23 241 to affect biochemical reactivities and stabilize tertiary structures 25,26). 

Poly(dG-dC) poly(dG-dC) and its methylated analogue structures assume left-handed conformation (Z-DNA) in high molar sodium salt (Na", K" ), in low molar divalent cations (Ca", Mg", Ni ), micromolar concentrations of hexaamine cobalt chloride (Co(NH3)6)Cl3 and in millimolar concentrations of polyamines. In order to analyse the binding of berberine to Z-form DNA, Kumar et al. [186] reported that the Z-DNA structure of poly(dG-dC) poly(dG-dC) prepared in either a high salt concentration (4.0 M) or in 40 mM (Co(NH3)6)Cl3 remained invariant in the presence of berberine up to a nucleotide phosphate/alkaloid molar ratio of 0.8 and suggested that berberine neither bormd to Z-form DNA nor converted the Z-DNA to the... 

The structures of polyamines are shown here as di-and tri-cations, but it should be realized that there are multiple positions for protonation and therefore various tautomers. Also, polyamines show extreme anti-cooperativity in proton binding, i.e., successive pKa values range from very low to very high for the last proton to leave. Polyamines are thought to have... 

The mechanisms by which antitumor-promoters suppress the tumor promotion are not known, but may be due to the following effects (i) inhibition of polyamine metabolism (ii) inhibition of arachidonic acid metabolism (iii) protease inhibition (iv) induction of differentiation (v) inhibition of oncogene expression (vi) inhibition of PKC and (vii) inhibition of oxidative DNA damage [3,6,91]. The polyamine content of cells is correlated to their proliferative, and often, their neoplastic capabilities. A key enzyme in the polyamine biosynthetic pathway, ornithine decarboxylase (ODC), catalyzes the convertion of ornithine to putrescine. Phorbol ester promoters such as TPA cause increased ODC activity and accumulation of polyamines in affected tissues. Diacylglycerol activated PKC, and the potent tumor promoter, TPA, binds to, and activates PKC, in competition with diacylglycerol. PKC stimulation results in phosphorylation of regulatory proteins that affect cell proliferation. Some chemopreventive agents have inhibitory activity towards PKC. Refer to recent review articles for further discussion [3,6,91]. 

B 9. Compare the structure of ethidium bromide (Figure E13.4) with those of the polyamines (Figure E13.5). Would you expect the binding of spermine or spermidine to DNA to be competitive with the binding of ethidium Explain. 

Spherical recognition of halide ions is displayed by protonated macropolycyclic polyamines. Thus, macrobicyclic diamines yield katapinates [3.9]. Anion cryptates are formed by the protonated macrobicyclic 16-6H+ [2.52] and macrotricyclic 21-4H+ [2.97] polyamines, with preferential binding of F and Cl- respectively in an octahedral and in a tetrahedral array of hydrogen bonds. 

Numerous processes may be linked to proton transfer and protonation/deprotonation reactions (for general descriptions of proton transfer see, for instance, [8.214-8.217]). Proton-triggered yes/no or +/- switching is contained in the ability of polyamine receptors and carriers to bind and transport cations when unproton-ated and anions when protonated also, zwitterions such as amino acids may change from bound to unbound or vice versa, when they undergo charge inversion as a function of pH. 

Polyamines are ubiquitous cell components essential for normal growth and maybe targets for therapeutic intervention (Marton and Pegg 1995). The protecting effects of polyamines is even more pronounced than that of proteins, such as, for example, the bacterial MCI protein or the lac suppressor to their binding sites (Isabelle et al. 1993, 1999). Multiply protonated polyamines such... 

Braunlin WH, StrickTJ, Record MT (1982) Eguilibrium dialysis studies of polyamine binding to DNA. Biopolymers 21 1301-1314... 

Vakurov et al. [46] evaluated a strategy to improve the covalent binding of AChE to screen-printed carbon electrodes modified with polyamines. To improve the extent of dialdehyde modification, electrodes were aminated. Initially, this was performed by electrochemical reduction of 4-nitrobenzenediazonium to a nitroaryl radical permitting attachment to the carbon surface subsequent reduction of the 4-nitrobenzene yielded a 4-aminobenzene-modified carbon surface. The obtained biosensors resulted in very sensitive devices measuring as low as 10 10 M of OPs. 

Thomas, T. J. and Thomas, T. (1994) Polyamine-induced Z-DNA conformation in plasmids containing (dA-dC)n(dG-dT) n inserts and increased binding of lupus autoantibodies to the Z-DNA form of plasmids. BiochemJ., 298,485—491. Tsumoto, T. and Yoshikawa, K. (1999) RNA switches the higher-order structure of DNA. Biophys. Chem., 82, 1-8. Ubbink, J. and Odijk, T. (1995) Polymer- and salt-induced toroids of hexagonal DNA. Biophys. J., 68, 54-61. 

Sacaan, A. I., andjohnson, K. M. (1990). Characterization of the stimulatory and inhibitory effects of polyamines on [3H] N-( -[thienyl] cyclohexyl) piperidine binding to the. V-methyl-D-aspartate receptor ionophore complex. Mol. Pharmacol. 37, 572—577. 

Peterson, A., Hancock, R.E.W., McGroarty, E.J., Binding of polycationic antibiotics and polyamines to lipopolysaccharides of Pseudomonas aeruginosa. J Bacteriol 164 (1985) 1256-1261. 

As for deaminase, the kinetic analysis suggests a partial mixed-type inhibition mechanism. Both the Ki value of the inhibitor and the breakdown rate of the enzyme-substrate-inhibitor complex are dependent on the chain length of the PolyP, thus suggesting that the breakdown rate of the enzyme-substrate-inhibitor complex is regulated by the binding of Polyphosphate to a specific inhibitory site (Yoshino and Murakami, 1988). More complicated interactions were observed between PolyP and two oxidases, i.e. spermidine oxidase of soybeen seedling and bovine serum amine oxidase. PolyP competitively inhibits the activities of both enzymes, but may serve as an regulator because the amino oxydases are also active with the polyamine-PolyP complexes (Di Paolo et al., 1995). 

A derivative of the (bpy.bpy.bpy) cryptand, obtained by modifying one of the chains, Lbpy, forms a di-protonated cryptate with EuCb in water at acidic pH, [EuCl3(H2Lbpy)]2+ in which the metal ion is coordinated to the four bipyridyl and two bridgehead nitrogen atoms, and to the three chlorine ions (Fig. 4.25). The polyamine chain is not involved in the metal ion coordination, due to the binding of the two acidic protons within this triamine subunit. In solution, when chlorides are replaced by perchlorate ions, two water molecules coordinate onto the Eu(III) ion at low pH and one at neutral pH, a pH at which de-protonation of the amine chain occurs, allowing it to coordinate to the metal ion. As a result, the intensity of the luminescence emitted by Eu(III) is pH dependent since water molecules deactivate the metal ion in a non-radiative way. Henceforth, this system can be used as a pH sensor. Several other europium cryptates have been developed as luminescent labels for microscopy. 

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