موسوی موحدی, علی اکبر and موسوی, سیدجعفر and دیوسالار, عادله and بابا احمدی, ابوذر and کریمیان, خشایار and شفیعی, عباس and کمره ای, محمود and پورساسان, نغمه and فرزامی, بیژن and ریاضی, غلام حسین and حکیم الهی, غلامحسین and تسای, فو یوان and احمد, فیضان and امانی, مجتبی and صبوری, علی اکبر (1388) اثرات دفریپرون و دفراسیروکس بر ساختار و عملکرد هموگلوبین بتا تالاسمی. Journal of Biomolecular Structure and Dynamics ــ 27 (3). pp. 319-329. شاپا 0739-1102
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Title
The effects of deferiprone and deferasirox on the structure and function of β-thalassemia hemoglobin
English Abstract
Transfusional iron overload is a major cause of morbidity and mortality in thalassemia, sickle-cell disease and other chronic anemias. To overcome these problems, orally bio available iron chelators, deferiprone and deferasirox, were used for the treatment of patients suffering from thalassemia. The interactions between deferiprone and deferasirox with the carrier protein, β-thalassemia hemoglobin (Hb), were investigated using fluorescence, circular dichroism (CD) and UV-visible measurements at physiological condition. Strong fluorescence quenching on interactions of the above drugs with β-thalassemia Hb were observed. Fluorescence quenching data of thalassemia Hb in the presence of deferasirox have shown greater affinity of binding. The number of binding sites to Hb for deferasirox was found to be more relative to those of the deferiprone. The effects of these drugs on the oxygen affinity of the thalassemia Hb were studied by spectroscopic methods using sodium dithionite. Results indicated that deferiprone reduces oxygen affinity (increases oxygen releasing ability) of Hb, while in the presence of deferasirox, oxygen affinity of Hb has significantly increased by dose-dependent manner. As such, deferasirox exhibited opposite effect relative to deferiprone on the function of thalassemia Hb. In clinical dose of deferiprone, CD results showed that, the α-helical content of thalassemia Hb significantly increased. By use of the clinical dose of deferasirox, however, a decrease in α-helical content of protein was observed, which resulted in decreasing stability of thalassemia Hb. Our study showed that reduction in stability of thalassemia Hb in the presence of deferasirox induced higher conformational changes in protein. ©Adenine Press (2009).
| Item Type: | Article |
|---|---|
| زبان سند : | انگلیسی |
| نویسنده مسئول : | علی اکبر موسوی موحدی |
| Additional Information: | cited By (since 1996) 0 1- Indexing: MEDLINE/PubMed 2- Scopus |
| کلیدواژه ها (انگلیسی): | beta thalassemia hemoglobin; deferasirox; deferiprone; hemoglobin; sodium dithionite; unclassified drug, article; beta thalassemia; binding affinity; circular dichroism; drug effect; fluorescence; human; human cell; oxygen affinity; priority journal; protein stability; ultraviolet radiation, Benzoic Acids; beta-Thalassemia; Circular Dichroism; Hemoglobins; Humans; Iron Chelating Agents; Pyridones; Spectrometry, Fluorescence; Structure-Activity Relationship; Triazoles |
| Subjects: | QU Biochemistry |
| Divisions: | Faculty of Medicine > Department of Basic Sciences > Department of Biophysics |
| ID Code: | 1830 |
| Deposited By: | Dr Mojtaba Amani |
| Deposited On: | 08 Sep 1389 01:47 |
| Last Modified: | 20 Jan 1393 12:47 |
Available Versions of this Item
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اثرات دفریپرون و دفراسیروکس بر ساختار و عملکرد هموگلوبین بتا تالاسمی. (deposited 18 Dec 1388 04:17)
- اثرات دفریپرون و دفراسیروکس بر ساختار و عملکرد هموگلوبین بتا تالاسمی. (deposited 08 Sep 1389 01:47) [Currently Displayed]
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