Протеолиз Простых Глипролинов Лейцинаминопептидазой, Ферментами Назальной Слизи, Мембран Мозга И Крови Крыс

Шевченко, К. В.; Вьюнова, Татьяна Владимировна; Нагаев, И. Ю.; Andreeva, L. A.; Мясоедов, Н.Ф.

doi:10.7868/s0132342313030159

Cited by 3 publications

(6 citation statements)

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“…Одним из этапов доклинических исследований при создании новых лекарственных препаратов является определение их устойчивости в условиях in vitro и in vivo [30][31][32].…”

Section: устойчивость пептидов In Vitrounclassified

“…Устойчивость пептидов [5-oxo-Pro-His-Pro-NH 2 , АКТГ(6-9)PGP, Pro-Gly-Pro-Leu и 5-охо-Pro-Arg-Pro] in vitro исследована с использованием лейцинаминопептидазы (КФ 3.4.11.2), карбоксипептидаз Y (КФ 3.4.16.1) и В (КФ 3.4.17.2), а также назальной слизи, микросомальной фракции мозга (МФМК) и плазмы крови крыс-самцов Wistar [31,32].…”

Section: устойчивость пептидов In Vitrounclassified

“…Пептиды инкубировали в присутствии указанных выше ферментов, и продукты реакции анализировали методом ВЭЖХ и масс-спектрометрии [23,[32][33][34][35][36].…”

Section: устойчивость пептидов In Vitrounclassified

“…Pro-Gly-Pro-Leu оказался более устойчивым к действию назальной слизи и плазмы крови. В присутствии МФМК и особенно лейцинаминопептидазы деградация Pro-Gly-Pro-Leu происходила более быстро [32]. Через инкубации в присутствии лейцинаминопептидазы из Pro-Gly-Pro-Leu образовывались Gly-Pro-Leu (57,0%), Pro-Gly-Pro (20,7%) и Gly-Pro (5,4%).…”

Section: устойчивость пептидов In Vitrounclassified

“…Проведённые эксперименты in vitro с перечисленными выше ферментными системами позволили определить и синтезировать, как и в случае АКТГ(6-9)PGP, возможные метаболиты этого пептида, что было необходимо для тестирования проб, полученных в экспериментах in vivo (рис. 4) [32]. Очевидно, что Gly-Pro-Leu образуется в результате гидролиза N-концевого пролина, а образование Gly-Pro происходит за счёт синхронного отщепления терминальных аминокислот от Pro-Gly-Pro-Leu.…”

Section: устойчивость пептидов In Vitrounclassified

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Stability of prolin-containing peptides in biological media

et al. 2019

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New data on peptide drugs have been summarized; their high stability is due to both the introduction of Pro-Gly-Pro in various amino acid sequences and the modification of the glyproline fragment itself. Pro-Gly-Pro-Leu, ACTH(6-9)Pro-Gly-Pro, 5-oxo-Pro-Arg-Pro and 5-oxo-Pro-His-Pro-NH2 were used as proline-containing peptides. Tritiated peptides were obtained: Pro-Gly-Pro-Leu with specific radioactivity of 135 Ci/mmol, ACTH(6-9)Pro-Gly-Pro – 26 Ci/mmol, 5-oxo-Pro-Arg-Pro – 60 Ci/mmol and 5-oxo-Pro-His-Pro-NH2 – 75 Ci/mmol. The concentration of Pro-Gly-Pro-Leu, ACTH(6-9)Pro-Gly-Pro, 5-oxo-Pro-Arg-Pro and 5-oxo-Pro-His-Pro-NH2 in the blood was found to be about 200 times more than in the brain for intranasal administration, and in average 600 times more for intravenous administration. The stability of proline-containing peptides in vitro experiments was determined using different commercially available peptidases (leucine aminopeptidases, dipeptidases, carboxypeptidases B and Y), and using nasal mucus, microsomal fraction of the rat brain (IMPC) and rat blood plasma. During peptidase hydrolysis of Pro-Gly-Pro-Leu, the main metabolites were Gly-Pro-Leu, Pro-Gly-Pro, Gly-Pro and Pro-Gly. For ACTH(6-9)Pro-Gly-Pro, the main metabolites were Phe-Arg-Trp-Pro-Gly-Pro and Trp-Pro-Gly-Pro. In peptidase hydrolysis of 5-oxo-Pro-His-Pro-NH2, the major metabolite was 5-oxo-Pro-His-Pro. It was shown that with different methods of peptides administration the composition of the metabolites formed is different. Based on the data obtained, resistance to enzymatic cleavage of peptides and their metabolic pathways were evaluated. Thus, these new data have shown that the above approaches can be used to prolong the action of glyprolines in living objects. In this case, the degradation of proline-containing peptides occurs mainly not due to the action of proteases, but due to other ways of degradation. In general, the data presented in the review indicate the promise of intranasal way of introducing biologically active peptides into the brain of living organisms.

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Section: устойчивость пептидов In Vitrounclassified

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Stability of prolin-containing peptides in biological media

et al. 2019

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Synthesis and Study of Properties of Phosphinic Pseudo-Prolylglycylproline

et al. 2021

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Study of stability of proline-containing derivatives of dopamine and serotonin in the biological media in vitro experiments

et al. 2019

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Boc-Gly-Pro-DP, Z-Gly-Pro-DP, LA-Gly-Pro-DP, Boc-Gly-Pro-Srt, Z-Gly-Pro-Srt were synthesized for the first time. The stability of these compounds in the presence of leucine aminopeptidase, carboxypeptidase Y, carboxypeptidase B and proline endopeptidase (PEP) was determined. It turned out that the compounds are stable in the presence of aminopeptidases and carboxypeptidases. In the presence of PEP, dopamine (DP) and serotonin (Srt) are cleaved from the synthesized preparations. Thus, new proline-containing Srt and DP derivatives were obtained, Srt and DP could be gradually released from them. This suggest the possibility of a prolonged action of these biologically active compounds on the vital activity of cells and, consequently, of the whole organism.

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Протеолиз Простых Глипролинов Лейцинаминопептидазой, Ферментами Назальной Слизи, Мембран Мозга И Крови Крыс

Cited by 3 publications

References 0 publications

Stability of prolin-containing peptides in biological media

Stability of prolin-containing peptides in biological media

Synthesis and Study of Properties of Phosphinic Pseudo-Prolylglycylproline

Study of stability of proline-containing derivatives of dopamine and serotonin in the biological media in vitro experiments

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