Studies on the interaction of chlorpromazine with haemoglobin.
01 Oct 1990-International Journal of Biological Macromolecules (Elsevier)-Vol. 12, Iss: 5, pp 297-301
TL;DR: The interaction of chlorpromazine (CPZ), a widely used antipsychotic tranquillizer, with the allosteric protein haemoglobin, has been studied by different methods and the possible nature of the binding site of the protein has been discussed on the basis of the information obtained from fluorescence measurements.
About: This article is published in International Journal of Biological Macromolecules.The article was published on 1990-10-01. It has received 12 citations till now. The article focuses on the topics: Cooperativity.
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TL;DR: Thermodynamic analysis revealed that binding of CPZ to hemoglobin was exothermic, whereas binding to myoglobin was endothermic with a high entropic contribution, suggesting that CPZ binding toMyoglobin is hydrophobic in nature.
68 citations
TL;DR: Binding modalities of chlorpromazine and trifluoperazine, two widely used antipsychotic phenothiazine drugs with hemoglobin and myoglobin have been studied to understand how the quaternary, tertiary and secondary structural organisations of the proteins regulate the binding process.
40 citations
TL;DR: Spectrophotometric studies reveal that protoporphyrin IX interacts with haemoglobin and myoglobin forming ground state complexes, which may have a role in establishing efficacy of therapeutic uses of porphyrins as well as in elucidating their mechanisms of action as therapeutic agents.
Abstract: Protoporphyrin IX and its derivatives are used as photosensitizers in the photodynamic therapy of cancer. Protoporphyrin IX penetrates into human red blood cells and releases oxygen from them. This leads to a change in the morphology of the cells. Spectrophotometric studies reveal that protoporphyrin IX interacts with haemoglobin and myoglobin forming ground state complexes. For both proteins, the binding affinity constant decreases, while the possible number of binding sites increases, as the aggregation state of the porphyrin is increased. The interactions lead to conformational changes of both haemoglobin and myoglobin as observed in circular dichroism studies. Upon binding with the proteins, protoporphyrin IX releases the heme-bound oxygen from the oxyproteins, which is dependent on the stoichiometric ratios of the porphyrin : protein. The peroxidase activities of haemoglobin and myoglobin are potentiated by the protein-porphyrin complexation. Possible mechanisms underlying the relation between the porphyrin-induced structural modifications of the heme proteins and alterations in their functional properties have been discussed. The findings may have a role in establishing efficacy of therapeutic uses of porphyrins as well as in elucidating their mechanisms of action as therapeutic agents.
37 citations
Cites methods from "Studies on the interaction of chlor..."
...Hb was isolated and purified by hemolysing the intact RBC and gel filtration (sephadex G-100) according to the method of Bhattacharyya et al (1990)....
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TL;DR: Spectrophotometric and spectrofluorimetric studies reveal that an interaction occurs between hemoglobin and hematoporphyrin, a photosensitizing drug used in photodynamic therapy, and appears to be predominantly electrostatic and enthalpy-driven in the lower range of porphyrIn concentration.
Abstract: Spectrophotometric and spectrofluorimetric studies reveal that an interaction occurs between hemoglobin and hematoporphyrin, a photosensitizing drug used in photodynamic therapy. Two concentration ranges of hematoporphyrin, 0.4–0.9 μM and 1.8–3.6 μM, representing significantly monomeric and aggregated (dimeric) state, respectively, have been used in the binding studies. The binding affinity constant ( K ) decreases, while the possible number of binding sites ( p ) increases as the concentration range of the porphyrin is increased. The nature of interaction has been studied by fluorescence quenching titration method under different ionic strengths and temperature conditions. It appears to be predominantly electrostatic and enthalpy-driven in the lower range of porphyrin concentration. However, the interaction follows mostly hydrophobic and entropy-driven modality in the higher concentration range of the ligand. The porphyrin-hemoglobin interaction results in release of oxygen from the protein. The extent of oxygen release depends on the stoichiometric ratio of hematoporphyrin: hemoglobin.
26 citations
TL;DR: The effect of porphyrins on heme proteins should be given due consideration in elucidating the details of the mechanism of p Morphyrin actions in therapy.
Abstract: Two important porphyrins, protoporphyrin IX and hematoporphyrin IX, derivatives of which form the basis of photosensitization in the photodynamic therapy of cancer treatment, interact with two physiologically important heme proteins hemoglobin and myoglobin. The extent and modality of these interactions vary with the state of aggregation of the two porphyrins. Upon binding with these proteins, both the drugs change the protein conformations and release the heme-bound oxygen from the oxyproteins. At the same time, the peroxidase activities of these proteins are potentiated due to the protein-porphyrin complexation, as is found in case of horseradish peroxidase also. The effect of porphyrins on heme proteins should be given due consideration in elucidating the details of the mechanism of porphyrin actions in therapy.
25 citations
References
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TL;DR: Human erythrocytes are protected or stabilized against hypotonic and mechanical hemolysis in the presence of low concentrations of many phenothiazines, reserpine, and haloperidol and the decrease in osmotic fragility may be explained possibly by an expansion of the cell membrane.
221 citations
TL;DR: The mechanisms by which chlorpromazine photosensitizes damage to membranes, protein and DNA are described and compared to the mechanisms of photosensitization by psoralens, porphyrins, dyes, and other molecules.
123 citations
TL;DR: The photoexcited chlorpromazine reacts with methanol to yield promazine and 2‐methoxypromazine by two different reaction pathways: hydrogen atom abstraction and nucleophilic attack respectively.
Abstract: — The photoexcited chlorpromazine reacts with methanol to yield promazine and 2-methoxypromazine by two different reaction pathways: hydrogen atom abstraction and nucleophilic attack. respectively. When the photoexcitation of chlorpromazine is performed in the presence of protein or nucleic acids, chlorpromazine binds to the biopolymer. This binding is drastically pH-dependent and correlates to the phototoxic effect exhibited in chlorpromazine—photosensitization of E. coli. No photodynamic damage of E. coli attributed to CPZ-sensitization of molecular oxygen could be detected.
61 citations
TL;DR: In xeroderma pigmentosum, an inherited disorder of defective DNA repair, post-UV colony-forming ability of fibroblasts from patients in complementation groups A through F correlates with the patients' neurological status, which is not significantly different from the curves of the group D fibroblast strains from patients with clinical histories similar to that of the Group G patient.
58 citations
TL;DR: Intensities of peaks further upfield than this peak, previously attributed to deoxy-alpha subunits, are difficult to measure directly especially for samples containing inositol hexaphosphate, which appears to increase with temperature.
44 citations