摘要:

AbstractA semi‐empirical model for quantitative structure‐time‐activity relationships (QSTAR) has been applied to the data on inhibition ofEscherichia coliin a batch culture in seven media of different acidity (pH 5.6 – 8.0) by twenty one nonionizable derivatives of kojic acid (5‐hydroxy‐2‐hydroxymethyl‐4H‐pyrane‐4‐one). The antibacterial potency of individual derivatives was characterized by the equieffective concentrations causing the 50%‐decrease in the specific growth rate in comparison with the untreated control. The QSTAR models satisfactorily describe toxicity of the studied compounds as a model‐based non‐linear function of hydrophobicity, the size of the substituents in the position 2, and the time of exposure. The dependence of the antibacterial activity on hydrophobicity at a fixed exposure time exhibits a broad maximum: the decrease for hydrophilic compounds is caused by their diminished ability for binding to the receptors and that for hydrophobic compounds is elicited by their lower concentrations in the aqueous phases and their slower inactivation. Inactivation is probably enzymatic because its rate depends on the size of the molecules. The size has a positive effect also on

ISSN:0931-8771    

DOI:10.1002/qsar.19960150202

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

摘要:

AbstractHuman lactoferrin displays considerable structural homology with transferrins of other species. However, lactoferrins and transferrins play distinct biological roles and bind to specific cell receptors. Previous reports have shown that residues 4 ‐ 52 of human lactoferrin are potentially involved in interaction with a specific T‐lymphocyte receptor. In the present study, competitive binding assays of lactoferrin to the Jurkat human lymphoblastic T‐cell line were performed using seven lactoferrins and transferrins, as well as both C‐terminal lobes of human and bovine lactoferrins. Classical quantitative structure‐affinity relationships (QSAR) models revealed important descriptors, namely H‐bonds donor and acceptor groups of amino acid side chains, demonstrating that hydrogen bonding is a significant binding factor. This report points out the importance of residues R3, Q7, P14, N13, T17, F20, Q23, R24, K28, S38, D43, S44, P45, Q47, Q50 and N55 of human lactoferrin in the interaction with the lymphocyte receptor. The most important residues which contribute positively to the inhibition of the binding affinity are R3, Q7, Q23, R24, S38, the chemical groups involved in H‐bonding are R3‐(NH), Q7‐(=O), Q23‐(=O),

ISSN:0931-8771    

DOI:10.1002/qsar.19960150203

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

摘要:

AbstractIt has previously been established that all or part of residues 4 ‐ 52 of human lactoferrin interact with the specific T‐lymphocyte receptor. Furthermore, the preliminary study using classical quantitative structure‐affinity relationships (QSAR) models have pointed out the importance of some H‐bond donor and acceptor groups of aminoacids in the interactions. In the present paper, comparative molecular field analysis (CoMFA) was used as a three‐dimensional QSAR method to define major steric and electrostatic features of lactoferrin‐T‐lymphocyte interactions. According to steric interaction energies, some residues of human lactoferrin: R3, F20, Q23, R24, S38 and Q47, previously described by the QSAR method, as well as Q21, R27 and R56 look essential for interactions. The results of the electrostatic features study are also in good agreement with the QSAR H‐bonds model and demonstrate that the pHi is a significant binding factor. Taken as a whole, QSAR and CoMFA methods allow to define two regions, potentially involved in selectivity between species, R3, Q7, N13, Q23, R24, S38, Q50 and N55; and binding potency, P14, F20, D43, S

ISSN:0931-8771    

DOI:10.1002/qsar.19960150204

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

摘要:

AbstractA set of 40 heteroaromatic systems was multivariately characterized by 13 descriptors derived by GRID. From this data matrix a second generation of Principal Properties for heteroaromatics was derived. Such Principal Properties are suitable for designing series of molecules of biological interest containing heteroaromatic moieties.

ISSN:0931-8771    

DOI:10.1002/qsar.19960150205

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

摘要:

AbstractEstimation of aqueous pKathrough quantum chemical gas‐phase and solution‐phase calculations is investigated for 16 carboxylic acids and 15 phenols with experimental data taken from literature. Parameters based on the AM1 hamiltonian include enthalpy and free energy differences between the ground state of the ionizable compounds and their anion counterparts as well as respective transition states and intermediates along the reaction path of the aqueous proton transfer. With carboxylic acids, additionalab initiocalculations are performed to evaluate the semiempirical level of theory. Aqueous solvation is modelled in three different ways: Application of continuum‐solvation methods AM1‐COSMO and AM1‐SM2, microsolvation of the solutes through formation of clusters with three water molecules, and combination of both approaches to include both bulk water polarization and solute‐solvent coupling effects. Regression equations withr adj2values up to 0.93 for carboxylic acids and 0.96 for phenols suggest, that continuum‐solvation models can be recommended to estimate aqueous pKathrough electronic structu

ISSN:0931-8771    

DOI:10.1002/qsar.19960150206

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19960150208

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19960150209

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19960150201

出版商:WILEY‐VCH Verlag    

年代:1996

数据来源: WILEY