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• W2509783516 abstract "Small peptides with a molecular weight of < 2 kDa represent a performance-enhancing substances. However, in vivo studies with human volunteers are limited because most of these peptides are not approved for human consumption. Thus, relevant in vitro models are a basic tool to study their metabolism for anti-doping purposes. To choose the best in vitro model the biotransformation of growth hormone releasing peptides (GHRPs), Desmopressin and TB-500 was investigated using various in vitro systems. High metabolic activity was observed during incubation of GHRPs and TB-500 with human kidney microsomes (HKM) and liver S9 fraction. Peptides degraded through cleavage of all bonds regardless protective modifications in primary structure. HKM and liver S9 fraction demonstrated enzymatic deamidation activity removing C-terminal amide group from all GHRPs. Fewer metabolites were produced during incubation with human serum. The metabolite pattern obtained with commercially available proteases was poor and included nonspecific hydrolyzed compounds. Thus, the maximum diversity of metabolites was achieved with HKM and liver S9 fraction which makes them the most efficient in vitro model systems for peptides biotransformation study. Currently, > 60 peptide medicines are FDA approved and marketed in the United States as biopharmaceutical products. Approximately 140 peptide drugs are in clinical trials and about 500 therapeutic peptides in preclinical development. There is an emerging interest in small peptides with a molecular weight of < 2 kDa, which can be used as doping in modern sport due a wide spectrum of their physiological activity. Most of peptide doping products are not yet approved for human use and some of them undergo preclinical or clinical trials, which complicates the study of metabolism in vivo. The investigation of the metabolism with in vitro methods is an alternative that does not require a human participation and an approval by the Ethics Committee." @default.
• W2509783516 created "2016-09-16" @default.
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• W2509783516 date "2016-10-01" @default.
• W2509783516 modified "2023-09-30" @default.
• W2509783516 title "Comparison of various in vitro model systems of the metabolism of synthetic doping peptides: Proteolytic enzymes, human blood serum, liver and kidney microsomes and liver S9 fraction" @default.
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• W2509783516 doi "https://doi.org/10.1016/j.jprot.2016.08.016" @default.
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