Lysine reactivity profiling reveals molecular insights into human serum albumin–small-molecule drug interactions

Yang, Shirui; Zhang, Wenxiang; Zhai, Ziyang; Hou, Xu-Dong; Wang, Ping; Ge, Guangbo; Wang, Fangjun

doi:10.1007/s00216-021-03700-1

Cited by 5 publications

(4 citation statements)

References 53 publications

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“…2B, the F/F 0 value of the HSA-MY-Phz system is higher than HSA-Phz system and lower than HSA-MY system. Since the binding constant of Phz/Ibf (10 5 M −1 ) is higher than MY (10 4 M −1 ), 45,46 Phz competes with MY with the adding of Phz, resulting in a complex system of HSA-MY and HSA-Phz. Thus, the F/F 0 value of HSA-MY-Phz complex system sits between the two blank systems when it reaches dynamic equilibrium.…”

Section: Resultsmentioning

confidence: 99%

Unveiling the binding details and esterase-like activity effect of methyl yellow on human serum albumin: spectroscopic and simulation study

Xia

Sun

et al. 2023

RSC Adv.

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Section: Resultsmentioning

confidence: 99%

Unveiling the binding details and esterase-like activity effect of methyl yellow on human serum albumin: spectroscopic and simulation study

Xia

Sun

et al. 2023

RSC Adv.

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“…amino acid residues of 190-200 of HSA was KASSAKQRLKC, while for rats, the sequence was VAAVRQRMKC. These 10 amino acid residues locate at a flexible region of HSA at the junction of domains 1 and 2, where have been found to bind with many kinds of drugs, including salicylate, glucose, warfarin, and antibiotics such as benzylpenicillin, piperacillin, amoxicillin, etc (Yvon et al, 1989;Tailor et al, 2016;Yang et al, 2021). We also analyzed the furmonertinib-protein adducts in rat plasma through gel separation and trypsin digestion.…”

Section: Species Differencementioning

confidence: 99%

Covalent Binding Mechanism of Furmonertinib and Osimertinib With Human Serum Albumin

Chen

et al. 2022

Drug Metab Dispos

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As third-generation tyrosine kinase inhibitors, furmonertinib and osimertinib exhibit better efficacy than first and second generation TKIs in patients with advanced non-small-cell lung cancer. However, radioactive pharmacokinetics studies showed that parent-related components remain in human plasma for at least 21 days after oral administration. Similar pharmacokinetic profiles were found in pyrotinib and neratinib, which have been identified to covalently bind with human serum albumin at Lys-190, leading to low extraction recovery in protein precipitation. However, the binding mechanism of Furmonertinib and Osimertinib in human plasma has not been confirmed. Comprehensive techniques were used to investigate the mechanism of this binding, including UHPLC coupled with HRMS and online/offline radioactivity profiling. SDS-PAGE and further autoradiography were also used to detect drug-protein adducts. We found that most furmonertinib exists in the human plasma following ex vivo incubation in the form of protein-drug adducts. Only lysine-furmonertinb adducts were found in pronase digests. A standard reference of lysine-furmonertinib was synthesized and confirmed by NMR. Through peptide mapping analysis, we confirmed that furmonertinib almost exclusively binds with HSA in plasma following ex vivo incubation, via Michael addition at Two peptides found to bond with furmonertinib were ASSAKQR and LKCASLQK.Osimertinib was also found to bond with Lys-195 and Lys-199 of HSA via peptide mapping analysis.

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“…As a prominent protein in blood plasma, human serum albumin (HSA) is essential for the transport of numerous molecules throughout the body [ 16 , 17 , 18 ]. HSA has different binding sites that interact with various compounds, including fatty acids, hormones, and drugs [ 19 , 20 ]. Its interaction with drugs is crucial, as it affects the distribution, metabolism, and bioavailability.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, HSA plays a vital role influencing their pharmacokinetics and pharmacodynamics [ 24 ]. The investigation of human serum albumin (HSA) and drug interactions has been greatly aided by molecular docking [ 19 , 25 ]. The technique of molecular docking enables the prediction of binding modes and affinity between drugs and HAS [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Exploration of Binding Affinities of a 3β,6β-Diacetoxy-5α-cholestan-5-ol with Human Serum Albumin: Insights from Synthesis, Characterization, Crystal Structure, Antioxidant and Molecular Docking

Alam

2023

Molecules

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The present study describes the synthesis, characterization, and in vitro molecular interactions of a steroid 3β,6β-diacetoxy-5α-cholestan-5-ol. Through conventional and solid-state methods, a cholestane derivative was successfully synthesized, and a variety of analytical techniques were employed to confirm its identity, including high-resolution mass spectrometry (HRMS), Fourier transforms infrared (FT-IR), nuclear magnetic resonance (NMR), elemental analysis, and X-ray single-crystal diffraction. Optimizing the geometry of the steroid was undertaken using density functional theory (DFT), and the results showed great concordance with the data from the experiments. Fluorescence spectral methods and ultraviolet–vis absorption titration were employed to study the in vitro molecular interaction of the steroid regarding human serum albumin (HSA). The Stern-Volmer, modified Stern-Volmer, and thermodynamic parameters’ findings showed that steroids had a significant binding affinity to HSA and were further investigated by molecular docking studies to understand the participation of active amino acids in forming non-bonding interactions with steroids. Fluorescence studies have shown that compound 3 interacts with human serum albumin (HSA) through a static quenching mechanism. The binding affinity of compound 3 for HSA was found to be 3.18 × 104 mol−1, and the Gibbs free energy change (ΔG) for the binding reaction was −9.86 kcal mol−1 at 298 K. This indicates that the binding of compound 3 to HSA is thermodynamically favorable. The thermodynamic parameters as well as the binding score obtained from molecular docking at various Sudlow’s sites was −8.2, −8.5, and −8.6 kcal/mol for Sites I, II, and III, respectively, supporting the system’s spontaneity. Aside from its structural properties, the steroid demonstrated noteworthy antioxidant activity, as evidenced by its IC50 value of 58.5 μM, which is comparable to that of ascorbic acid. The findings presented here contribute to a better understanding of the pharmacodynamics of steroids.

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Lysine reactivity profiling reveals molecular insights into human serum albumin–small-molecule drug interactions

Cited by 5 publications

References 53 publications

Unveiling the binding details and esterase-like activity effect of methyl yellow on human serum albumin: spectroscopic and simulation study

Unveiling the binding details and esterase-like activity effect of methyl yellow on human serum albumin: spectroscopic and simulation study

Covalent Binding Mechanism of Furmonertinib and Osimertinib With Human Serum Albumin

Exploration of Binding Affinities of a 3β,6β-Diacetoxy-5α-cholestan-5-ol with Human Serum Albumin: Insights from Synthesis, Characterization, Crystal Structure, Antioxidant and Molecular Docking

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