Interaction of drugs with bovine and human serum albumin
TL;DR: Fluorescence emission spectra of serum albumin in the presence of MMI or PTU, recorded at the excitation wavelengths 280 and 295 nm, clearly show that the studied drugs act as quenchers.
About: This article is published in Journal of Molecular Structure.The article was published on 2002-09-02. It has received 789 citations till now. The article focuses on the topics: Bovine serum albumin & Human serum albumin.
Citations
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TL;DR: The data establish a direct link among AA, Tet, and DNA methylation, thus revealing a role of AA in the regulation of DNA modifications.
Abstract: DNA hydroxymethylation and its mediated DNA demethylation are critical for multiple cellular processes, for example, nuclear reprogramming, embryonic development, and many diseases. Here, we demonstrate that a vital nutrient ascorbic acid (AA), or vitamin C (Vc), can directly enhance the catalytic activity of Tet dioxygenases for the oxidation of 5-methylcytosine (5mC). As evidenced by changes in intrinsic fluorescence and catalytic activity of Tet2 protein caused by AA and its oxidation-resistant derivatives, we further show that AA can uniquely interact with the C-terminal catalytic domain of Tet enzymes, which probably promotes their folding and/or recycling of the cofactor Fe2+. Other strong reducing chemicals do not have a similar effect. These results suggest that AA also acts as a cofactor of Tet enzymes. In mouse embryonic stem cells, AA significantly increases the levels of all 5mC oxidation products, particularly 5-formylcytosine and 5-carboxylcytosine (by more than an order of magnitude), leadi...
479 citations
TL;DR: Experimental results showed that the binding of GEM to BSA or HSA induced conformational changes in BSA and HSA, and confirmed that the secondary structure of protein was altered by GEM.
477 citations
TL;DR: The results point to a static quenching mechanism operating in the complexes of 2-Pyridone, 3-pyridones, and 4-p Pyridone that is typical of tryptophan in a polar environment and are slightly reduced upon probe binding.
Abstract: Subdomain IIA binding site of human serum albumin (HSA) was characterized by examining the change in HSA fluorescence in the native, unfolded, and refolded states. The study was carried out in the absence and presence of small molecular probes using steady-state and time-resolved fluorescence measurements. 2-Pyridone, 3-pyridone, and 4-pyridone bear similar molecular structures to those found in many drugs and are used here as probes. They are found to specifically bind in subdomain IIA and cause a reduction in the fluorescence intensity and lifetime of the Trp-214 residue in native HSA which is located in the same subdomain. The efficiency of energy transfer from Trp-214 fluorescence to the probes was found to depend on the degree of the spectral overlap between the donor's fluorescence and the acceptor's absorption. After probe binding in subdomain IIA, the distance between the donor and acceptor was calculated using Forster theory. The calculated quenching rate constants and binding constants were also shown to depend on the degree of spectral overlap. The results point to a static quenching mechanism operating in the complexes. Denaturation of HSA in the presence of guanidine hydrochloride (GdnHCl) starts at [GdnHCl] > 1.0 M and is complete at [GdnHCl] > or = 6.0 M. Upon unfolding, two fluorescence peaks were observed. One peak was assigned to the fluorescence of Trp-214 in a polar environment, and the other peak was assigned to tyrosine fluorescence. A reduction of the fluorescence intensity of the two peaks upon binding of the probes to the denatured HSA indicates that Tyr-263 in subdomain IIA is one of the tyrosine residues responsible for the second fluorescence peak. The results were confirmed by measuring the fluorescence spectra and lifetimes of denatured HSA at different excitation wavelengths, and of L-tryptophan and L-tyrosine free in buffer. The measured lifetimes of denatured HSA are typical of tryptophan in a polar environment and are slightly reduced upon probe binding. Dilution of the denatured HSA by buffer results in a partial refolding of subdomain IIA. This partial refolding is attributed to some swelling of the binding site caused by water. The swelling prevents a full recovery from the denatured state.
455 citations
TL;DR: The interactions of chlorogenic acid and ferulic acid with human serum albumin (HSA) have been investigated by fluorescence and Fourier transformed infrared (FT-IR) spectrometry and indicated a partial unfolding of HSA in the presence of the two acids.
429 citations
TL;DR: The β-LG conformation was altered in the presence of polyphenols with an increase in β-sheet and α-helix suggesting protein structural stabilisation, which can be used to explain the mechanism by which the antioxidant activity of tea compounds is affected by the addition of milk.
383 citations
References
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TL;DR: A review of the use of the technique of solute fluorescence quenching to study the structure and dynamics of proteins and a number of factors are discussed that must be considered in analyzing such data.
1,644 citations
TL;DR: The crystal structure of HSA complexed with five molecules of myristate at 2.5 Å resolution is determined and it is shown that fatty acid molecules bind in long, hydrophobic pockets capped by polar side chains, many of which are basic.
Abstract: Human serum albumin (HSA) is the most abundant protein in the circulatory system. Its principal function is to transport fatty acids, but it is also capable of binding a great variety of metabolites and drugs. Despite intensive efforts, the detailed structural basis of fatty acid binding to HSA has remained elusive. We have now determined the crystal structure of HSA complexed with five molecules of myristate at 2.5 A resolution. The fatty acid molecules bind in long, hydrophobic pockets capped by polar side chains, many of which are basic. These pockets are distributed asymmetrically throughout the HSA molecule, despite its symmetrical repeating domain structure.
1,291 citations
TL;DR: The experimental data show that both the protonated (HA) and ionized (A-) forms of BA can distribute in 1-octanol, and consequently a partition coefficient for HA (logP' HA) and for A- ( logP' A-) must be defined.
185 citations
TL;DR: Scheek et al. as mentioned in this paper used 2D NOE spectroscopy to identify the resonances of water-exchangeable imino protons in NMR spectra of oligonucleotides.
141 citations
TL;DR: There are virtually no data on the effects of maternal PTU on thyroid status of infants whose mothers take more than 300 mg PTU daily and who are wholly breast‐feeding.
Abstract: BACKGROUND
Propylthiouracil (PTU) might theoretically be preferred over methimazole (MMI) during breast-feeding because of its lower milk/serum concentration ratio (0.1 vs. 1.0). The problem is that Graves' disease often relapses during the postpartum period, and high doses of PTU are sometimes needed to control maternal hyperthyroidism) during breast-feeding. However, there are virtually no data on the effects of maternal PTU on thyroid status of infants whose mothers take more than 300 mg PTU daily and who are wholly breast-feeding.
OBJECTIVES
To investigate whether mothers can breast-feed without adverse effects on infants' thyroid status while taking 300 mg or more daily of PTU .
SUBJECTS AND DESIGN
Eleven infants who were wholly breast-fed while their mothers took PTU 300–750 mg daily for Graves' hyperthyroidism were included in this study. In one of the 11 infants, the mother also took iodine 6 mg daily for a limited period. Thyroid status in these infants was evaluated.
MEASUREMENTS
Free T4 (FT4), thyrotrophin (TSH), and TSH binding inhibiting antibody (TBIAb) concentrations were examined at least once in the age range 6 days to 9 months. Maternal blood was also examined for FT4 and TBIAb on the same day, or within a week, of the infants' blood tests. FT4, TSH and TBIAb concentrations at birth were examined, using cord blood, in cases where antithyroid drugs had been continued through delivery.
RESULTS
Three of the 11 infants had TSH concentrations higher than the normal range for adults. In one of the three infants, the TSH concentration, which was determined 19 weeks after birth, was just above the normal range. In the remaining two infants whose mothers had taken PTU through delivery, TSH concentrations, determined within 7 days after birth, were distinctly high, but they became normal while maternal PTU doses were the same as or higher than those at the initial examination. Maternal PTU doses or FT4 concentrations were not significantly correlated with infants' TSH concentrations.
CONCLUSION
Mothers can breast-feed while taking propylthiouracil at doses as high as 750 mg daily without adverse effects on thyroid status in their infants.
76 citations