Excessive labeling technique provides a highly sensitive fluorescent probe for real-time monitoring of biodegradation of biopolymer pharmaceuticals in vivo

S. S. Terekhov, I. V. Smirnov, O. G. Shamborant, M. A. Zenkova, E. L. Chernolovskaya, D. V. Gladkikh, A. N. Murashev, I. A. Dyachenko, V. D. Knorre, A. A. Belogurov, N. A. Ponomarenko, S. M. Deyev, V. V. Vlasov, A. G. Gabibov

Результат исследований: Материалы для журналаСтатья

Выдержка

Recombinant proteins represent a large sector of the biopharma market. Determination of the main elimination pathways raises the opportunities to significantly increase their half-lives in vivo. However, evaluation of biodegradation of pharmaceutical biopolymers performed in the course of pre-clinical studies is frequently complicated. Noninvasive pharmacokinetic and biodistribution studies in living organism are possible using proteins conjugated with near-infrared dyes. In the present study we designed a highly efficient probe based on fluorescent dye self-quenching for monitoring of in vivo biodegradation of recombinant human butyrylcholinesterase. The maximum enhancement of integral fluorescence in response to degradation of an intravenously administered enzyme was observed 6 h after injection. Importantly, excessive butyrylcholinesterase labeling with fluorescent dye results in significant changes in the pharmacokinetic properties of the obtained conjugate. This fact must be taken into consideration during future pharmacokinetic studies using in vivo bioimaging.

Язык оригиналаАнглийский
Страницы (с-по)54-59
Число страниц6
ЖурналActa Naturae
Том6
Номер выпуска23
СостояниеОпубликовано - 2014
Опубликовано для внешнего пользованияДа

Отпечаток

Biopolymers
Pharmacokinetics
Biodegradation
Fluorescent Dyes
Labeling
Butyrylcholinesterase
Monitoring
Pharmaceutical Preparations
Recombinant Proteins
Quenching
Coloring Agents
Fluorescence
Infrared radiation
Degradation
Injections
Enzymes
Proteins

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology

Цитировать

Terekhov, S. S., Smirnov, I. V., Shamborant, O. G., Zenkova, M. A., Chernolovskaya, E. L., Gladkikh, D. V., ... Gabibov, A. G. (2014). Excessive labeling technique provides a highly sensitive fluorescent probe for real-time monitoring of biodegradation of biopolymer pharmaceuticals in vivo. Acta Naturae, 6(23), 54-59.

Excessive labeling technique provides a highly sensitive fluorescent probe for real-time monitoring of biodegradation of biopolymer pharmaceuticals in vivo. / Terekhov, S. S.; Smirnov, I. V.; Shamborant, O. G.; Zenkova, M. A.; Chernolovskaya, E. L.; Gladkikh, D. V.; Murashev, A. N.; Dyachenko, I. A.; Knorre, V. D.; Belogurov, A. A.; Ponomarenko, N. A.; Deyev, S. M.; Vlasov, V. V.; Gabibov, A. G.

В: Acta Naturae, Том 6, № 23, 2014, стр. 54-59.

Результат исследований: Материалы для журналаСтатья

Terekhov, SS, Smirnov, IV, Shamborant, OG, Zenkova, MA, Chernolovskaya, EL, Gladkikh, DV, Murashev, AN, Dyachenko, IA, Knorre, VD, Belogurov, AA, Ponomarenko, NA, Deyev, SM, Vlasov, VV & Gabibov, AG 2014, 'Excessive labeling technique provides a highly sensitive fluorescent probe for real-time monitoring of biodegradation of biopolymer pharmaceuticals in vivo', Acta Naturae, том. 6, № 23, стр. 54-59.
Terekhov SS, Smirnov IV, Shamborant OG, Zenkova MA, Chernolovskaya EL, Gladkikh DV и соавт. Excessive labeling technique provides a highly sensitive fluorescent probe for real-time monitoring of biodegradation of biopolymer pharmaceuticals in vivo. Acta Naturae. 2014;6(23):54-59.
Terekhov, S. S. ; Smirnov, I. V. ; Shamborant, O. G. ; Zenkova, M. A. ; Chernolovskaya, E. L. ; Gladkikh, D. V. ; Murashev, A. N. ; Dyachenko, I. A. ; Knorre, V. D. ; Belogurov, A. A. ; Ponomarenko, N. A. ; Deyev, S. M. ; Vlasov, V. V. ; Gabibov, A. G. / Excessive labeling technique provides a highly sensitive fluorescent probe for real-time monitoring of biodegradation of biopolymer pharmaceuticals in vivo. В: Acta Naturae. 2014 ; Том 6, № 23. стр. 54-59.
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AU - Terekhov, S. S.

AU - Smirnov, I. V.

AU - Shamborant, O. G.

AU - Zenkova, M. A.

AU - Chernolovskaya, E. L.

AU - Gladkikh, D. V.

AU - Murashev, A. N.

AU - Dyachenko, I. A.

AU - Knorre, V. D.

AU - Belogurov, A. A.

AU - Ponomarenko, N. A.

AU - Deyev, S. M.

AU - Vlasov, V. V.

AU - Gabibov, A. G.

PY - 2014

Y1 - 2014

N2 - Recombinant proteins represent a large sector of the biopharma market. Determination of the main elimination pathways raises the opportunities to significantly increase their half-lives in vivo. However, evaluation of biodegradation of pharmaceutical biopolymers performed in the course of pre-clinical studies is frequently complicated. Noninvasive pharmacokinetic and biodistribution studies in living organism are possible using proteins conjugated with near-infrared dyes. In the present study we designed a highly efficient probe based on fluorescent dye self-quenching for monitoring of in vivo biodegradation of recombinant human butyrylcholinesterase. The maximum enhancement of integral fluorescence in response to degradation of an intravenously administered enzyme was observed 6 h after injection. Importantly, excessive butyrylcholinesterase labeling with fluorescent dye results in significant changes in the pharmacokinetic properties of the obtained conjugate. This fact must be taken into consideration during future pharmacokinetic studies using in vivo bioimaging.

AB - Recombinant proteins represent a large sector of the biopharma market. Determination of the main elimination pathways raises the opportunities to significantly increase their half-lives in vivo. However, evaluation of biodegradation of pharmaceutical biopolymers performed in the course of pre-clinical studies is frequently complicated. Noninvasive pharmacokinetic and biodistribution studies in living organism are possible using proteins conjugated with near-infrared dyes. In the present study we designed a highly efficient probe based on fluorescent dye self-quenching for monitoring of in vivo biodegradation of recombinant human butyrylcholinesterase. The maximum enhancement of integral fluorescence in response to degradation of an intravenously administered enzyme was observed 6 h after injection. Importantly, excessive butyrylcholinesterase labeling with fluorescent dye results in significant changes in the pharmacokinetic properties of the obtained conjugate. This fact must be taken into consideration during future pharmacokinetic studies using in vivo bioimaging.

KW - Biodegradation

KW - Butyrylcholinesterase

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KW - In vivo bioimaging

KW - Pharmacokinetics

KW - Proteolysis

KW - Self-quenching

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