Search

The interaction of 17 monoamine oxidase inhibitory drugs (propargylamine derivatives) with amino acids was studied by charge-transfer chromatography. The data set was evaluated by principal component analysis (PCA). To assess the effect of the information loss caused by normalization, PCA was separately carried out on the covariance and on the correlation matrix. The strength and selectivity of interaction was separated by the spectral mapping technique. Calculation proved that the amino group of the drugs interacted with the second carboxyl group of dicarboxylic amino acids, and that the interaction was of electrostatic character. This finding made probable the direct interaction between the drugs and the target enzyme or enzymes. The results of both PCA methods were similar. However, coordinates of the spectral map showed only slight correlation with the corresponding coordinates of the two-dimensional nonlinear maps proving the different information content of the methods.

The effect of 21 nucleoside derivatives on the [3H]-thymidine cellular uptake and on the incorporation into DNA of highly metastatic 3LL (Lewis lung carcinoma) cells has been measured. Hydrophobic and hydrophilic molecular parameters (the adsorption capacity, specific adsorption surface, lipophilicity and specific hydrophobic surface area) have been determined by using thin-layer chromatography. Stepwise linear regression analysis and principal component analysis have been applied in order to reveal the relationships between the molecular parameters and the effect of the nucleoside derivatives on highly metastatic 3LL cells. The first principal component obtained from the measured activity data could be attributed to the change of [3H]-thymidine cellular uptake caused by the nucleoside, while the second principal component could be regarded as the measure of the effect on the DNA incorporation of [3H]-thymidine. The effect of the nucleosides on the [3H]-thymidine uptake could be explained by the specific hydrophobic and adsorption surface area of the nucleoside, on the other hand the effect on the DNA incorporation could be described by the adsorption characteristics (specific hydrophilic surface area and adsorption capacity) of the derivatives.

The absorption capacity, the specific hydrophilic surface area, the lipophilicity and the specific hydrophobic surface area of 17 monoamine oxidase inhibitory drugs were determined by means of adsorptive and reversed-phase thin-layer chromatography for future application of these molecular parameters in quantitative structure-activity relationship studies. Principal component analysis suggests that most of the physicochemical parameters have a different information content, and their application in the elucidation of their mode of action is therefore justified.

The retentions of 28 peptides in reversed-phase thin-layer chromatography (RPTLC) were determined on cellulose and on impregnated cellulose and alumina layers with 1-propanol as the organic component of the mobile phase. Each peptide showed a support matrix effect: their RM values first decreased to a minimum, then increased with increasing 1-propanol concentration. On cellulose layers only the increasing phase was observed. The retention behaviour of peptides was adequately described with a quadratic or linear function, but the slope value of the linear function had a positive value. The results demonstrate that the support matrix effect can be observed on non-silica supports and it may occur in reversed-phase chromatography in the case of polar solutes and supports with free adsorptive centres on their surfaces. Both the intercept and slope values of the function are needed to describe the lipophilicity of peptides, but the correlation is not strong enough for the determination of the lipophilicity of peptides by RPTLC. Principal component analysis showed that the peptides form distinct clusters on the basis of their retention characteristics: peptides containing a basic amino acid, peptides with a ring structure in the amino acid side-chain and peptides containing uncharged amino acids.

1. The review deals with the recent achievements in the study of the various interactions of phospholipids with proteins and peptides. 2. The interactions are classified according to the hydrophobic, hydrophilic or mixed character of the interactive forces. 3. The effect of the interaction on the structure and biological activity of the interacting molecules is also discussed.

The lipophilicity (RM value) of seventeen monoamine oxidase inhibitory drugs was determined by reversed-phase thin-layer chromatography, and the effect of salt concentration on the reversed-phase retention was studied by adding ammonium chloride to the eluent. Each drug exhibited regular retention behaviour, its RM value linearly decreasing with increasing concentration of methanol in the eluent. Ammonium chloride decreased the retention: the effect was higher at lower salt concentrations, which indicates that the phenomenon is of saturation character. The influence of ammonium chloride depended on the concentration of methanol (on the dielectric constant of the eluent) suggesting that methanol suppresses the dissociation of ammonium chloride resulting in a modified salting-in effect.

The interaction of dipalmitoylphosphatidylcholine, dipalmitoylphosphatidic acid and dipalmitoylphosphatidylethanolamine with some DNA substructures such as cytidine, uridine, adenosine 5'di- and triphosphate, guanosine 5'mono- and diphosphate, cytidine 5'mono- and triphosphate, uridine 5'mono- and triphosphate and inosine 5'monophosphate was studied with differential scanning calorimetry. The dependence of pretransition and main transition temperatures and the enthalpy of main transition on the molecular characteristics of the interacting molecular species was calculated by stepwise regression analysis. Nucleosides and nucleotides increased the main transition temperature and peak half width of phospholipids and they decreased the enthalpy of main transition proving the existence of interaction between phospholipids and DNA substructures. Calculation proved that the interaction is mainly of hydrophilic character but the involvement of hydrophobic forces or steric conditions cannot be ruled out.

The effect of chlorhexidine and its molecular complexes with some nonionic tenzides (Tween and Myrj series) on the phase transfer parameters of dipalmitoylphosphatidylcholine has been studied by differential scanning calorimetry. The application of principal component analysis facilitated the evaluation of the experimental data matrix. It was found that both the lipophilicity of the tenzide and the strength of interaction between chlorhexidine and nonionic tenzide had a considerable impact on some of the phase transition parameters of dipalmitoylphosphatidylcholine. These findings indicate the possible existence of ternary complexes. This ternary complex formation may cause a decrease of chlorhexidine activity in the presence of nonionic tenzides.

The interaction of the bipyridylium herbicides diquat and paraquat with the proteins gliadin and human serum albumin (HSA) as well as with cellulose and the effect of various ions on the strength of interaction were studied by charge-transfer chromatography. Both compound showed very similar behaviour. The ions decreased in each case the strength of interaction, the effect depended nonlinearly on the ion concentration and was of saturation character. Gliadin showed the weakest interaction. HSA binds the bipyridylium compounds in an ion-dependent manner, the strength of interaction is higher than that of cellulose at higher ion concentration. This finding indicates an ion-mediated interaction of unknown character between the bipyridylium herbicides and HSA.

1. The review deals with the recent achievements in the study of the various interactions of phospholipids with proteins, peptides and amino acids. The interactions are classified according to the hydrophobic, hydrophilic or mixed character of the interactive forces. The effect of the interaction on the structure and biological activity of the interacting biomolecules is discussed.

The retention of twelve 2-nitro-4-cyanophenyl esters showing marked herbicidal activity was determined in 23 reversed-phase thin-layer chromatographic systems. The retention data set was evaluated by principal component analysis (PCA). To assess the effect of the information loss caused by normalization, PCA was separately carried out on the covariance (method A) and on the correlation matrix (method B). The ratio of the variances explained was very similar for both methods, however, the PC loadings and the coordinates of the two-dimensional nonlinear maps showed poor correlation. The distribution of the 2-nitro-4-cyanophenyl esters and that of chromatographic systems showed differences on the two-dimensional nonlinear maps of PC loadings and PC variables, however, the general trend was similar independently of the application of method A or B. The findings indicate that the application of the correlation matrix as basis for the PCA calculations may lead to slightly distorted results that strongly advocates the use of covariance matrix in PCA.

The lipophilicities of 22 peptides were determined by reversed-phase thin-layer chromatography using methanol as organic modifier in the concentration range 0-90 vol.-% on silica supports with surface pH values of 2.0,4.5,6.0,7.5 and 9.0. Only one of the 22 peptides (Trp-Ala-Ile) followed the general rule, i.e., its RM value decreased linearly with increasing proportion of organic modifier over the whole concentration range. Most peptides exhibited typical silanophilic retention behaviour, the RM value decreasing with increasing organic phase concentration in the lower concentration range and then increasing with further increase in the proportion of organic modifier. In some instances the lipophilicity increased linearly with increasing proportion of methanol. The silanophilic effect depended not only on the structure of the peptide, but also on the surface pH of the silica support. The retention behaviour of peptides can be well described by a polynomial function, the linear and quadratic forms of methanol concentration and surface pH being the independent variables. Principal component analysis showed that the presence of a ring structure in the peptides has the greatest impact on their retention behaviour, the overall polarity (basic, neutral or acidic) being of secondary importance. The number of amino acids in the peptide has a negligible effect on the chromatographic behaviour.

The interactions of chlorhexidine with 42 nonionic tensides were studied by means of charge-transfer reversed-phase thin-layer chromatography. The alkyl chain of chlorhexidine interacted with the alkyl chains in the hydrophobic part of the tensides, while the ethylene oxide groups of the tensides interacted with the polar guanidine groups of chlorhexidine. These two types of interaction (hydrophobic and hydrophilic) are probably not independent of each other.

The interaction between oppositely charged amino acids was studied by charge-transfer reversed-phase thin-layer chromatography. The dependence of the lipophilicity of Arg, Lys and Orn on the concentration of Glu, Asp, Gln and Asn in the eluent was considered to be related to the strength of interaction. The interaction of dibasic amino acids with Glu and Asp was stronger than with Gln and Asn. Mono- (Li+, Na+, K+, Rb+ and Cs+) and divalent (Mg2+ and Ca2+) cations decreased the strength of interaction suggesting the electrostatic character of the interaction. Their inhibitory effect mainly depended on their concentration and to a lesser extent on the ion charge and hydrated ion radii. Stepwise regression analysis proved that the strength of interaction depends on the polarity parameters of amino acids and is independent of their chemical structure.

The paper deals with the recent achievements in the study of the various interactions between proteins, peptides and amino acids. The interactions are classified according to the hydrophilic, hydrophobic or mixed character of the interactive forces. The effect of the interaction on protein (peptide) association, structure and biological activity as well as the role of individual amino acid residues in the hydrophobic and hydrophilic interactions are discussed.

Auxin interacts with dibasic amino acids forming charge-transfer complexes. The interaction is of hydrophilic character, the strength of interaction increasing with the logarithm of auxin concentration. Sodium, potassium, magnesium and calcium ions decrease the strength of interaction, while their inhibitory effect increases with increasing concentration and ion charge.

The adsorption capacity, the specific adsorptive surface, the lipophilicity and the specific hydrophobic surface of 59 natural and synthetic nucleoside derivatives were determined by means of adsorptive chromatography and reversed-phase thin-layer chromatography for the future application of these molecular parameters in quantitative structure-activity relationship studies. Stepwise regression analysis and principal component analysis proved that each of the physico-chemical parameters has a different information content, and their application in the design of new bioactive derivatives is therefore justified.

The interaction between amino acids was studied by charge-transfer reversed-phase thin-layer chromatography. The dependence of the lipophilicity of Trp on the concentration of other amino acids in the eluent was considered to be linearly related to the strength of interaction. Arg, Asn, Glu, Met, Phe and Thr interacted with Trp; Ala, Gly and Ser showed no interaction. Stepwise regression analysis indicated that the pK value of the amino acid side-chain and the lipophilicity of the amino acid had the greatest impact on the interaction, suggesting the simultaneous presence of weak hydrophilic and hydrophobic bonding forces between amino acids. Sodium acetate in the eluent increased the interactive strength between Phe and Trp; acetic acid and sodium chloride did not influence the interaction significantly. No significant difference was found between the effects of L- and D-Asn.

To gain more insight in mode of action of ten different 4-hydroxy-benzonitrile derivatives, their biological activities in eight bioassays, and their lipophilicity and adsorptivity determined by thin-layer chromatography in nine different systems were subjected to principal component analysis. Four background components explained about 90% of total variance. Only three of eight biological activities, the inhibition of the 2,6-dichlorophenol-indophenol reduction by spinach and wheat chloroplasts and the CO2 fixation of wheat seedlings had not any common background components with the physico-chemical parameters of the compounds. The nonlinear mapping of principal component loadings and variables showed, that the in vivo and in vitro biological activities differed considerably and depended on the object investigated. The effectivity of compounds is governed mainly by the number of substituents and by the presence of free hydroxy group.

The effect of ion strength and pH value of the eluent on the determination of the lipophilicity of chlorhexidine was studied by reversed-phase thin-layer chromatography. The method has been improved by using various buffers: aqueous solutions of formic, acetic and propionic acids and their sodium salts in different ratios and in various concentrations. Stepwise regression analysis separated the effect of pH value, ion strength and acid type on the lipophilicity of chlorhexidine and proved that the ion strength exerted a higher impact than the pH value did. The effect of alkyl chain length of the acids was of secondary importance.

The retention order of methylated lysine and arginine derivatives followed a reversed-phase separation pattern on various silicas with aqueous salt solutions used as eluents. Principal component analysis established that the origin of the silica exerts a dominant influence on their chromatographic performance, and the effect of impregnation and salt quality are of secondary importance. Good linear correlations were found between the lipophilicity-decreasing effect of monovalent cations and their ionic radii.