Binding affinities of folic acid and related pterins with biological macromolecules under physiological conditions

Pteridines ◽  
2015 ◽  
Vol 26 (1) ◽  
pp. 23-29
Author(s):  
Michael Soniat ◽  
Christopher B. Martin

AbstractFolic acid and pterin derivatives are important heterocyclic compounds found in a variety of biological systems and have been shown to be photochemically active. Understanding the amount of binding that various pterins have with biological macromolecules under physiological conditions is important in predicting what specific biomolecules will bind with pterins and may, therefore, result in photochemical damage from charge-transfer reactions. The relative binding of folic acid, or pteroyl-L-glutamic acid (PteGlu), 6-methylpterin (Mep), 6-hydroxymethylpterin (Hmp), 6-formylpterin (Fop), and 6-carboxypterin (Cap) with bovine serum albumin (BSA), electrically neutral lipid (ENL), polyguanylic acid (Poly G), polycytidylic acid (Poly C), polyadenylic acid (Poly A), polythymidylic acid (Poly T), Micrococcus luteus DNA (72% GC), Escherichia coli DNA (50% GC), calf thymus DNA (42% GC), and Clostridium perfrigens DNA (27% GC) in neutral phosphate buffer were studied. Our results indicate that PteGlu demonstrated strong binding to neutral lipids, while the other pterins showed minimal binding, and BSA had a significant binding to PteGlu, Cap, and especially Fop. Our results also reveal a high affinity for DNA by PteGlu, which suggests that a relatively high percentage of folic acid is bound to DNA before photochemistry occurs.

1969 ◽  
Vol 114 (4) ◽  
pp. 679-687 ◽  
Author(s):  
A. M. Q. King ◽  
B. H. Nicholson

1. The interaction of aflatoxin B1 with different polynucleotides was studied spectrophotometrically. Equations were derived that enable the degree of binding to be determined without first determining the extinction coefficient of the bound form. 2. The interaction with calf thymus DNA obeys first-order relationships with an association constant of 0·40mm−1, but there is some evidence for a secondary binding process from results obtained at 390nm. 3. The spectral shifts decreased in the order polyadenylic acid+polyuridylic acid>DNA>polyadenylic acid>polyadenylic acid+polyinosinic acid. Polycytidylic acid, polyuridylic acid, polyinosinic acid (both single- and triple-stranded), AMP, CMP, GMP and UMP did not interact with aflatoxin. It was concluded that there is a requirement for the amino group of adenine (or possibly guanine) for binding of aflatoxin to polynucleotides to occur. 4. Binding is reversed by increasing ionic strength, and by Mn2+ and Mg2+ in the concentration range studied (0–5mm). The effect of the Mn2+ or Mg2+ was far greater than would be expected on the basis of their ionic strength. With both the bivalent cations and sodium chloride the reversal is greatest with double-stranded polynucleotides. 5. Inhibition in vitro of the DNA-dependent RNA polymerase of Escherichia coli by aflatoxin B1 was detected only in the absence of Mg2+ and at concentrations of Mn2+ below the optimum for RNA synthesis in vitro. 6. The degree of inhibition (maximally 30%) was dependent on the concentration of Mn2+ and decreased during incubation.


1997 ◽  
Vol 71 (4) ◽  
pp. 325-332 ◽  
Author(s):  
U. Pandya ◽  
J.K. Saxena ◽  
O.P. Shukla

AbstractThe interaction of DNA from filarial parasite Setaria cervi with polyamines was monitored by melting temperature (Tm) profile, condensation and B to Z DNA transition and compared with DNA of Escherichia coli, Micrococcus luteus and calf thymus having different GC content. Polyamines, viz. spermine and spermidine, stabilized the secondary structure of all DNAs as indicated by increase in Tm value. UV absorption studies indicated B to Z DNA transition in the presence of polyamines. The amount of polyamines required for B to Z transition was dependent upon base composition of DNA and charge of the polyamine. Filarial DNA (AT rich) required six times higher concentration of spermine as compared to GC rich DNA for B to Z DNA transition. Spermidine was not effective in causing transition of S. cervi DNA even at Spd:DNA-P ratio of 20. The antifilarial compound suramin significantly decreased melting temperature of filarial DNA as compared to GC rich DNAs of other parasites. Suramin adversely affected condensation and B to Z DNA transition of various DNAs but prior addition of polyamines protected the DNAs from the destabilizing effect of suramin.


2016 ◽  
Vol 27 (15) ◽  
pp. 2368-2380 ◽  
Author(s):  
Po-Lin Yang ◽  
Tzu-Han Hsu ◽  
Chao-Wen Wang ◽  
Rey-Huei Chen

The neutral lipids steryl ester and triacylglycerol (TAG) are stored in the membrane-bound organelle lipid droplet (LD) in essentially all eukaryotic cells. It is unclear what physiological conditions require the mobilization or storage of these lipids. Here, we study the budding yeast mutant are1Δ are2Δ dga1Δ lro1Δ, which cannot synthesize the neutral lipids and therefore lacks LDs. This quadruple mutant is delayed at cell separation upon release from mitotic arrest. The cells have abnormal septa, unstable septin assembly during cytokinesis, and prolonged exocytosis at the division site at the end of cytokinesis. Lipidomic analysis shows a marked increase of diacylglycerol (DAG) and phosphatidic acid, the precursors for TAG, in the mutant during mitotic exit. The cytokinesis and separation defects are rescued by adding phospholipid precursors or inhibiting fatty acid synthesis, which both reduce DAG levels. Our results suggest that converting excess lipids to neutral lipids for storage during mitotic exit is important for proper execution of cytokinesis and efficient cell separation.


2021 ◽  
Author(s):  
Sahar Qazi ◽  
Bimal Prasad Jit ◽  
Abhishek Das ◽  
Muthukumarasamy Karthikeyan ◽  
Amit Saxena ◽  
...  

The POTE family comprises 14 paralogues and is primarily expressed in Prostrate, Placenta, Ovary, Testis, Embryo (POTE), and cancerous cells. The prospective function of the POTE protein family under physiological conditions is less understood. We systematically analyzed their cellular localization and molecular docking analysis to elucidate POTE proteins' structure, function, and Adaptive Divergence. Our result discerns that group three POTE paralogs (POTEE, POTEF, POTEI, POTEJ, and POTEKP (a pseudogene)) exhibits significant variation among other members could be because of their Adaptive Divergence. Furthermore, our molecular docking studies on POTE protein revealed the highest binding affinity with NCI-approved anticancer compounds. Additionally, POTEE, POTEF, POTEI, and POTEJ were subject to an explicit molecular dynamic simulation for 50ns. MM-GBSA and other essential electrostatics were calculated that showcased that only POTEE and POTEF have absolute binding affinities with minimum energy exploitation. Thus, this study's outcomes are expected to drive cancer research to successful utilization of POTE genes family as a new biomarker, which could pave the way for the discovery of new therapies.


2021 ◽  
Author(s):  
Tina P. Andrejević ◽  
◽  
Darko P. Ašanin ◽  
Nada D. Savić ◽  
Nevena Lj. Stevanović ◽  
...  

In recent decades, a special attention has been devoted to gold(III) complexes as potential antitumor agents due to their structural similarity to platinum(II) complexes. One of the possible mechanisms of the mode of antitumor activity of gold(III) complexes could include their interaction with DNA. However, the effectiveness of the therapeutic agents also depends on the degree of its binding to proteins present in the blood plasma, because, in this way, it is transported to the cell. Considering this, we investigated the interactions of three dinuclear gold(III) complexes of the general formula [{AuCl3}2(μ– L)], L = 4,4’-bipy (4,4’-bipyridine, Au1), bpe (1,2-bis(4-pyridyl)ethane, Au2) and dpe (1,2-bis(4- pyridyl)ethene, Au3) with calf thymus DNA (ct-DNA) and bovine serum albumin (BSA). The main aim of the study was to evaluate the binding affinities of gold(III) complexes Au1–3 towards these biomolecules for possible insights on their mode of biological activity. The values of binding constants (KA) of Au1–3 to ct-DNA are higher than those for BSA, indicating greater affinity of the complexes towards this nucleic acid. The partition coefficient (logP) value for Au1 is higher compared to the corresponding values for the other two complexes, what is in accordance with a higher cellular uptake efficiency of this complex.


Biopolymers ◽  
2004 ◽  
Vol 75 (5) ◽  
pp. 403-411 ◽  
Author(s):  
Kazuya Koumoto ◽  
Ryouji Karinaga ◽  
Masami Mizu ◽  
Takahisa Anada ◽  
Kazuo Sakurai ◽  
...  

The Analyst ◽  
2015 ◽  
Vol 140 (8) ◽  
pp. 2823-2833 ◽  
Author(s):  
Xuheng Jiang ◽  
Kui Gao ◽  
Daopan Hu ◽  
Huanhuan Wang ◽  
Shujuan Bian ◽  
...  

Voltammetric studies on the simple ion transfer (IT) behaviors of an important water-soluble B-vitamin, folic acid (FA), at the liquid–liquid (L–L) interface were firstly performed and applied as a novel detection method for FA under physiological conditions. This work provides a new and attractive strategy for the detection of FA− and other biological anions.


1969 ◽  
Vol 47 (6) ◽  
pp. 637-642 ◽  
Author(s):  
Fred H. Wolfe ◽  
Kimio Oikawa ◽  
Cyril M. Kay

The ultraviolet circular dichroism spectra of polyadenylic acid, polyguanylic acid, polycytidylic acid, polyinosinic acid, and polyuridylic acid have been examined at neutral and acidic pH values, and at moderate and low ionic strengths, over the wavelength range 300–185 mμ. Increased resolution of spectra below 225 mμ has revealed heretofore unexamined ellipticity bands in the low wavelength region, which are sensitive to conformational alterations for those polynucleotides which exhibit both single and multistranded secondary structures. It is concluded that these ellipticity bands, in view of their extreme sensitivity to conformation, will be of significance in increasing the usefulness of the homopolynucleotides as model compounds in conformational studies of naturally occurring RNAs.


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