Molecular Recognition Studies on Naphthyridine Derivatives

Iglesias-Sánchez, José Carlos; María, Dolores Santa; Claramunt, Rosa M.; Elguero, José

doi:10.3390/molecules15031213

Cited by 10 publications

(7 citation statements)

References 19 publications

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“…Purification of the crude material by flash chromatography eluting with 5% methanol in CH 2 Cl 2 gave the target compound as a white solid (52 mg, 78%). Spectral data are in agreement with those reported in the literature (Iglesias-Sánchez et al, 2010).…”

Section: Biotin Iodidesupporting

confidence: 91%

“…The reported procedure ( Martin-Serrano, 2018 ) was followed ( Iglesias-Sánchez et al, 2010 ). Biotin tosylate (75 mg, 0.196 mmol) and NaI (60 mg, 0.391 mmol) were stirred at reflux in acetone (10 mL) for 24 h. The solvent was removed under reduced pressure and the residue was dissolved in CH 2 Cl 2 and the organic layer was successively washed with aqueous saturated sodium thiosulfate (10 mL) and water, dried over anhydrous Mg 2 SO 4 , and concentrated in vacuo.…”

Section: Methodsmentioning

confidence: 99%

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Biotin-Labelled Clavulanic Acid to Identify Proteins Target for Haptenation in Serum: Implications in Allergy Studies

et al. 2020

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Clavulanic acid (CLV) and amoxicillin, frequently administered in combination, can be independently involved in allergic reactions. Protein haptenation with β-lactams is considered necessary to activate the immune system. The aim of this study was to assess the suitability of biotinylated analogues of CLV as probes to study protein haptenation by this β-lactam. Two synthetic approaches afforded the labeling of CLV through esterification of its carboxylic group with a biotin moiety, via either direct binding (CLV-B) or tetraethylenglycol linker (CLV-TEG-B). The second analogue offered advantages as solubility in aqueous solution and potential lower steric hindrance for both intended interactions, with the protein and with avidin. NMR reactivity studies showed that both CLV and CLV-TEG-B reacts through β-lactam ring opening by aliphatic amino nitrogen, however with different stability of resulting conjugates. Unlike CLV conjugates, that promoted the decomposition of clavulanate fragment, the conjugates obtained with the CLV-TEG-B remained linked, as a whole structure including biotin, to nucleophile and showed a better stability. This was a desired key feature to allow CLV-TEG-B conjugated protein detection at great sensitivity. We have used biotin detection and mass spectrometry (MS) to detect the haptenation of human serum albumin (HSA) and human serum proteins. MS of conjugates showed that HSA could be modified by CLV-TEG-B. Remarkably, HSA preincubation with CLV excess only reduced moderately the incorporation of CLV-TEG-B, which could be attributed to different protein interferences. The CLV-TEG-B fragment with opened β-lactam was detected bound to the 404–430HSA peptide of the treated protein. Incubation of human serum with CLV-TEG-B resulted in the haptenation of several proteins that were identified by 2D-electrophoresis and peptide mass fingerprinting as HSA, haptoglobin, and heavy and light chains of immunoglobulins. Taken together, our results show that tagged-CLV keeps some of the CLV features. Moreover, although we observe a different behavior in the conjugate stability and in the site of protein modification, the similar reactivity indicates that it could constitute a valuable tool to identify protein targets for haptenation by CLV with high sensitivity to get insights into the activation of the immune system by CLV and mechanisms involved in β-lactams allergy.

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Section: Biotin Iodidesupporting

confidence: 91%

Section: Methodsmentioning

confidence: 99%

Biotin-Labelled Clavulanic Acid to Identify Proteins Target for Haptenation in Serum: Implications in Allergy Studies

et al. 2020

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“…In an attempt to go further in the understanding of the effect of the fluorine atom position on the inhibitory activity, a statistical analysis of the results was carried out using a Free–Wilson matrix [72,73,74,75,76] (see Supplementary Files) differentiating the fluorine atoms according to their position. Considering that compounds 1 , 7 – 11 of the first series are 20 times less potent than those of the second series, we have divided their percentages of inhibition by 20 and have reported the normalized values together with those of the second series of pyrazoles 12 – 16 , in Table 5.…”

Section: Resultsmentioning

confidence: 99%

Fluorination Effects on NOS Inhibitory Activity of Pyrazoles Related to Curcumin

et al. 2015

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“…and the independent variables F, Cl, and Br (I is the reference) lead to a series of equations where the coefficients of the halogens are their individual contributions. For a more complete discussion of the use of Free-Wilson or presence-absence matrices, see [74][75][76][77][78][79][80].…”

Section: Halogen Atoms Comparisonsmentioning

confidence: 99%

The SN2 reaction and its relationship with the Walden inversion, the Finkelstein and Menshutkin reactions together with theoretical calculations for the Finkelstein reaction

Alkorta

Elguero

2021

Struct Chem

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This communication gives an overview of the relationships between four reactions that although related were not always perceived as such: SN2, Walden, Finkelstein, and Menshutkin. Binary interactions (SN2 & Walden, SN2 & Menshutkin, SN2 & Finkelstein, Walden & Menshutkin, Walden & Finkelstein, Menshutkin & Finkelstein) were reported. Carbon, silicon, nitrogen, and phosphorus as central atoms and fluorides, chlorides, bromides, and iodides as lateral atoms were considered. Theoretical calculations provide Gibbs free energies that were analyzed with linear models to obtain the halide contributions. The M06-2x DFT computational method and the 6-311++G(d,p) basis set have been used for all atoms except for iodine where the effective core potential def2-TZVP basis set was used. Concerning the central atom pairs, carbon/silicon vs. nitrogen/phosphorus, we reported here for the first time that the effect of valence expansion was known for Si but not for P. Concerning the lateral halogen atoms, some empirical models including the interaction between F and I as entering and leaving groups explain the Gibbs free energies.

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Molecular Recognition Studies on Naphthyridine Derivatives

Cited by 10 publications

References 19 publications

Biotin-Labelled Clavulanic Acid to Identify Proteins Target for Haptenation in Serum: Implications in Allergy Studies

Biotin-Labelled Clavulanic Acid to Identify Proteins Target for Haptenation in Serum: Implications in Allergy Studies

Fluorination Effects on NOS Inhibitory Activity of Pyrazoles Related to Curcumin

The SN2 reaction and its relationship with the Walden inversion, the Finkelstein and Menshutkin reactions together with theoretical calculations for the Finkelstein reaction

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