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SEARCH OF NEW PHARMACEUTICALS ON THE BASIS OF DARBEPOETIN IN THE TREATMENT OF ISCHEMIC STROKE (REVIEW OF LITERATURE)

The article contains the analysis of medical and biological publications from the global database created by the National Centre for Biology Information (NCBI), an intramural biotechnological division of the US National Library of Medicine. The authors have analyzed publications of the recent ten years. Major results of study of erythropoietins and their recombinant analogues have been generalized and systematized. There has been revealed the significant potential of the preparations of this group to be studied and used. Major advantages and drawbacks of erythropoietins and their recombinant analogues have been described. It has been pointed out that a great variety of erythropoietins and darbepoetins speaks to the fact that there is lack of “universe” erythropoietin meeting all the requirements. Genetically modified erythropoietin having both - pharmacokinetics convenient for clinical application and all properties of the natural analogue - is considered to be the most successful darbepoetin. This property has been resulted from the fact that comparing to standard erythropoietin darbepoetin has bigger molecular weight due to introduction of 2 complementary sites of glycosylation. This, in turn, results in the increase of half-life period and, consequently, decreases application frequency of the preparation that makes it more convenient to use comparing to erythropoietin. Application of erythropoietin and its derivatives in stroke therapy in experimental animal models undoubtedly has positive impact on the reduction of the infarction size and dynamics of recovery of neurological status. Results of the analysis demonstrate that the studied preparations are more effective in the early period following stroke than being applied in the later hours. However, there has been revealed some insufficient knowledge in treatment of brain ischemic lesions and ischemic heart disease.

Ключевые слова: erythropoietin, darbepoetin, stroke.

Иллюстрации

Figure 1. Amino acid sequence of the darbepoetin alpha molecule (replacement of 5 amino acids in polypeptide chain by the method of site-directed mutagenesis allowed creating 5 sites of glycosylation, two of which are in positions 30 and 80). Adapted from Lin F-K et al. Proc Natl Acad Sci USA. 1985; 82: 7580-7584 and Elliot S. et al. Nature Biotechnol. 2003; 21: 414-421.

Figure 2. Comparing structures of darbepoetin alpha (on the right) and rHuEPO (on the left) molecules. Arrows show 2 complementary tetra-antenna N-linked carbon chains that led to more erythropoietic activity of darbepoetin due to prolongation of half-life period (explanations are given in the text). Adapted from Sinclair AM, Elliot S, 2005. 

Table 1. Comparative characteristic of  rHuEPO alpha and beta and darbepoetin alpha (adapted from Deicher R, Horl WH, 2004)

 

DOI: 10.18413/2500-235X-2017-3-1-125-136
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