β-lactam antibiotics epitope mapping with STD NMR spectroscopy: a study of drug-human serum albumin interaction

Abstract

Eventos de reconhecimento molecular são questões chave em muitos processos biológicos. O experimento de STD NMR (ressonância magnética nuclear por diferença de transferência de saturação) é uma das técnicas usadas para se entender tais interações biológicas. Neste trabalho, foram investigadas as interações entre quatro antibióticos β-lactâmicos pertencentes às classes das cefalosporinas e penicilinas com a albumina de soro humano (HSA) através de STD NMR de 1 H. Nossos resultados indicam que a interação entre o anel aromático destes antibióticos e HSA é responsável pela eficiência da ligação. Assim, as diferenças estruturais entre os tio-anéis de cinco dos seis membros das penicilinas e cefalosporinas parecem não influenciar as interações do antibiótico com a albumina.Molecular recognition events are key issues in many biological processes. STD NMR (saturation transfer difference nuclear magnetic resonance spectroscopy) is one of the techniques used to understand such biological interactions. Herein, we have investigated the interactions of four β-lactam antibiotics belonging to two classes (cephalosporins and penicillins) with human serum albumin (HSA) by 1 H STD NMR revealing that the interaction between the aromatic moiety and HSA is responsible for the binding efficiency. Thus, the structural differences from the five to six-membered thio ring in penicillins and cephalosporins do not seem to influence antibioticalbumin interactions.

Cephalosporin as Potent Urease and Tyrosinase Inhibitor: Exploration through Enzyme Inhibition, Kinetic Mechanism, and Molecular Docking Studies

“…Enzymes, mushroom tyrosinase, and urease were purchased from Sigma. Eleven drugs from cephalosporin class were purchased from local pharmacy, and their active ingredients were summarized in Table 1 and Figure S1 with formula [17][18][19][20][21][22][23][24][25][26][27]. To prepare stock, ground powder was weighted to directly dissolve in DMSO.…”

Anaphylaxis to drugs: Overcoming mast cell unresponsiveness by fake antigens

“…The attachment of a drug to a protein occurs first via non-covalent bonds (Table 1 and Figure 1). [14][15][16] These are the dominant type of intermolecular forces in supra-molecular chemistry and rely on van der Waals forces, electrostatic interac- After an initial non-covalent binding, the drug may bind by a covalent bond to a certain amino acid within the protein (Figure 1). This feature depends on the chemical property of the drug.…”

“…The attachment of a drug to a protein occurs first via non‐covalent bonds (Table 1 and Figure 1). 14‐16 These are the dominant type of intermolecular forces in supra‐molecular chemistry and rely on van der Waals forces, electrostatic interactions, ion pairs, and hydrogen pairs. Even though they are weak individually, their cumulative energies of molecular interactions can be significant.…”

Structural Elucidation of β‐Lactam Diastereoisomers through Ion Mobility Mass Spectrometry Studies and Theoretical Calculations

“…β‐Lactams are most frequently studied by chromatographic methods such as high‐performance liquid chromatography mass spectrometry (MS), high‐performance liquid chromatography with fluorescent detection and ion‐pair liquid chromatography . Other analytical methods available to analyze isomeric β‐lactams are ultraviolet–visible spectroscopy, calorimetry and nuclear magnetic resonance spectroscopy . These methods provide high specificity and sensitivity for quantitative multiresidue analysis; nevertheless, the differentiation among β‐lactam isomers still remains a challenging task.…”

“…[9] Other analytical methods available to analyze isomeric β-lactams are ultraviolet-visible spectroscopy, [10] calorimetry [11] and nuclear magnetic resonance spectroscopy. [12,13] These methods provide high specificity and sensitivity for quantitative multiresidue analysis; nevertheless, the differentiation among β-lactam isomers still remains a challenging task. Therefore, in this work, we applied ion mobility technique coupled to mass spectrometry (IM-MS) to separate and characterize isomeric structures of selected β-lactams.…”