Lipophilicity and antiproliferative activity profiling of 2-benzylidencycloalkanones.

High performance liquid chromatographic (HPLC) method has been developed to separate the members of a library including 24 benzylidenecycloalkanone-type structures and to characterize their lipophilicity. The experimental lipophilicity data (k) of the compounds have been compared with their calculated lipophilicity parameters (CLOGP). In general, good correlations between the measured and calculated lipophilicities have been found and these results were in good accordance with our previously data obtained in case of structurally related molecular libraries. In addition, cytotoxicity screening has been performed to determine the antiproliferative activity of these compounds. Some of the investigated compounds possessed noticeable inhibitory potential. Based on the correlation between the antiproliferative activity and experimentally determined lipophilicity of the molecules investigated, limited structural demands to obtain more potent compounds can be exhibited to support the synthetic design.

Effect of D-amino acids at Asp23 and Ser26 residues on the conformational preference of Abeta20-29 peptides.

The effects of d-amino acids at Asp(23) and Ser(26) residues on the conformational preference of beta-amyloid (Abeta) peptide fragment (Abeta(20-29)) have been studied using different spectroscopic techniques, namely vibrational circular dichroism (VCD), vibrational absorption, and electronic circular dichroism. To study the structure of the Abeta(20-29), [d-Asp(23)]Abeta(20-29), and [d-Ser(26)]Abeta(20-29) peptides under different conditions, the spectra were measured in 10mM acetate buffer (pH 3) and in 2,2,2-trifluoroethanol (TFE). The spectroscopic results indicated that at pH 3, Abeta(20-29) peptide takes random coil with beta-turn structure, while [d-Ser(26)]Abeta(20-29) peptide adopts significant amount of polyproline II (PPII) type structure along with beta-turn contribution and d-Asp-substituted peptide ([d-Asp(23)]Abeta(20-29)) adopts predominantly PPII type structure. The increased propensity for PPII conformation upon d-amino acid substitution, in acidic medium, has important biological implications. In TFE, Abeta(20-29), [d-Asp(23)]Abeta(20-29), and [d-Ser(26)]Abeta(20-29) peptides adopt 3(10)-helix, alpha-helix, and random coil with some beta-turn structures, respectively. The VCD data obtained for the Abeta peptide films suggested that the secondary structures for the peptide films are not the same as those for corresponding solution and are also different among the Abeta peptides studied here. This observation suggests that dehydration can have a significant influence on the structural preferences of these peptides.

Micellar proportion: a parameter to compare the hydrophobicity of the pseudostationary phases or that of the analytes in micellar electrokinetic chromatography.

Micellar proportion, t(prop,mic) = t(mic)/t(m), a quantity expressing how much time is spent by the analyte in the micellar phase related to its whole migration time (t(m)) has been introduced by utilizing the micellar phase residence time (t(mic)). The t(prop,mic) values have been determined for analytes of different chemical structures (alkyl benzene and alkyl phenone homologous series, alcohols, strongly hydrophobic peptides) studied by micellar elektrokinetic chromatography (MEKC) using various cationic and anionic pseudostationary phases. A good linear correlation was obtained between t(prop,mic) and the calculated hydrophobicity (CLOGP) of the analytes for all pseudostationary phases (CLOGP = A.logt(prop,mic) + B). Considering a given pseudostationary phase, t(prop,mic) as a relative quantity is a suitable parameter to characterize and compare experimentally the behavior of the various analytes in MEKC. Applying a set of probe molecules with known hydrophobicity, the CLOGP(50) value (showing the value of hydrophobicity of a virtual molecule spending exactly 50% of its migration time in the pseudostationary phase) has been calculated for each pseudostationary phase applied here. This experimentally determinable numerical value (characterizing the pseudostationary phase) can be utilized to compare the hydrophobicity and hence retention ability of the pseudostationary phases. The t(prop,mic) value was found to be applicable to compare the methylene selectivity of the different pseudostationary phases as well: logt(prop,mic) = A.Z + B, where Z is the number of carbon atoms of the alkyl chain in the alkyl benzene homologous series.

Separation of anti-tumor peptides by capillary electrophoresis in organic solvent containing background electrolytes.

Connections between the calculated and measured electrophoretic mobilities (nu(ep)) determined by capillary electrophoresis as well as connections between the measured and calculated diffusion coefficients of anti-tumor peptides have been investigated in background electrolytes (BGEs) containing different organic solvents (acetonitrile, methanol, ethanol and isopropanol). Comparison of the electrophoretic mobility (nu(ep)) values revealed discrepancies between the measured and calculated values. However, no change in the migration order or selectivity could be expected from the calculated nu(ep) values, variation of both properties was observed applying organic solvents as BGE modifiers. Experimental determination of the diffusion coefficient suggested that the effect of the organic solvents is not restricted to the change of the BGE viscosity. The reason for the discrepancy between the measured and calculated mobility values might be the possible conformation and/or solvation changes of the peptide caused by the different organic solvents.