TY  - JOUR
AU  - Jelkmann, Wolfgang
A2  - Jelkmann, Wolfgang
DB  - BISp
DP  - BISp
KW  - Blutdoping
KW  - Doping
KW  - Dopinganalyse
KW  - Dopingbekämpfung
KW  - Erythropoetin
KW  - Hämatologie
KW  - Protein
KW  - Stimulans
KW  - Tierversuch
LA  - eng
TI  - Erythropoiesis stimulating agents and techniques : a challenge for doping analysts
TT  - Stimulanz-Wirkstoffe und Techniken der Erythropoese : Anknüpfungspunkte für Dopinganalytiker
PY  - 2009
N2  - Recombinant human erythropoietin (rHuEPO) engineered in Chinese hamster ovary (CHO) cell cultures (Epoetin alfa and Epoetin beta) and its hyperglycosylated analogue Darbepoetin alfa are known to be misused by athletes. The drugs can be detected by isoelectric focusing (IEF) and immunoblotting of urine samples, because “EPO” is in reality a mixture of isoforms and the N-glycans of the recombinant products differ from those of the endogenous hormone. However, there is a plethora of novel erythropoiesis stimulating agents (ESAs). Since the originator Epoetins alfa and beta are no longer protected by patent in the European Union, rHuEPO biosimilars have entered the market. In addition, several companies in Asia, Africa and Latin America produce copied rHuEPOs for clinical purposes. While the amino acid sequence of all Epoetins is identical, the structure of their glycans differs depending on the mode of production. Some products contain more acidic and others more basic EPO isoforms. Epoetin delta is special, as it was engineered by homologous recombination in human fibrosarcoma cells (HT-1080), thus lacking N-glycolylneuraminic acid like native human EPO. ESAs under development include EPO fusion proteins, synthetic erythropoiesis stimulating protein (SEP) and peptidic (HematideTM, CNTO 528) as well as non-peptidic EPO mimetics. Furthermore, preclinical respectively clinical trials have been performed with small orally active drugs that stimulate endogenous EPO production by activating the EPO promoter (“GATA-inhibitors”: diazepane derivatives) or enhancer (“HIF-stabilizers”: 2-oxoglutarate analogues). The prohibited direct EPO gene transfer may become a problem in sports only in the future.    Verf.-Referat
SP  - S. 1236-1247
SN  - 0929-8673
JO  - Current medicinal chemistrychemistry
IS  - 10
VL  - 16
M3  - Gedruckte Ressource
ID  - PU201007005529
ER  -