47 research outputs found
Retention parameters of some isomeric 2-benzoylbenzoic acids in reversed-phase ion-pair high performance thin-layer and column chromatography
Structural effects and retention in reversed-phase ion-pair chromatography of 2-benzoylbenzoic acid derivatives
Comparison of chromatographic parameters of heterocyclic bases and their N-oxides in liquid-liquid partition systems
In silico approach in the assessment of chromatographic parameters as descriptors of diphenylacetamides' biological/pharmacological profile
The selected diphenylacetamide derivatives were subjected to chromatographic and in silico approach in order to obtain significant information about their structure-activity relationships. As an early step in the assessment of their biological profile, drug-likeness and lead-likeness rules were performed, as well as determination of the bioactivity scores. The relationships between the obtained chromatographic parameters and the relevant software lipophilicity/pharmacokinetic/toxicity predictors of the studied derivatives were examined by linear regression and multivariate methods. Beside the satisfactory linear relationships obtained for each applied system, the multivariate methods gave more concrete relations between the analyzed parameters of biological activity. Higher similarity between the chromatographic parameters (R (M) (0), C (0)), standard measure of lipophilicity and pharmacokinetic predictors was confirmed, while the chromatographic parameter m obtained in the same conditions exhibits better agreement with the bioactivity scores and toxicity parameters. Also, it was observed that the values of diphenylacetamide's biological activity parameters are in the greatest extent conditioned by the polarity of the substituent presented in its molecule
The effect of reactions of the carbonyl group on the chromatographic parameters of organic compounds in liquid-liquid partition systems
Chromatographic retention data of N-alkylamides of benzomorpholine-2-carboxylic acid in the study of structure-activity relationships
Conformational Melding Permits a Conserved Binding Geometry in TCR Recognition of Foreign and Self Molecular Mimics
Molecular mimicry between foreign and self antigens is a mechanism of T cell receptor cross-reactivity and is thought to contribute to the development of autoimmunity. The αÎČ TCR A6 recognizes the foreign antigen Tax from the virus HTLV-1 when presented by the class I MHC HLA-A2. In a possible link with the autoimmune disease HAM/TSP, A6 also recognizes a self peptide from the neuronal protein HuD in the context of HLA-A2. We found here that the complexes of the HuD and Tax epitopes with HLA-A2 are close but imperfect structural mimics, and that in contrast with other recent structures of TCRs with self antigens, A6 engages the HuD antigen with the same traditional binding mode used to engage Tax. Although peptide and MHC conformational changes are needed for recognition of HuD but not Tax and the difference of a single hydroxyl triggers an altered TCR loop conformation, TCR affinity towards HuD is still within the range believed to result in negative selection. Probing further, we found that the HuD/HLA-A2 complex is only weakly stable. Overall, these findings help clarify how molecular mimicry can drive self/non-self cross-reactivity and illustrate how low peptide/MHC stability can permit the survival of T cells expressing self-reactive TCRs that nonetheless bind with a traditional binding mode