Excessive Labeling Technique Provides a Highly Sensitive Fluorescent Probe for Real-time Monitoring of Biodegradation of Biopolymer Pharmaceuticals in vivo

S. S. Terekhov; Терехов С. С.; I. V. Smirnov; Смирнов И. В.; O. G. Shamborant; Шамборант О. Г.; M. A. Zenkova; Зенкова М. А.; E. L Chernolovskaya; Черноловская Е. Л.; D. V. Gladkikh; Гладких Д. В.; A. N. Murashev; Мурашев А. Н.; I. A. Dyachenko; Дьяченко И. А.; V. D. Knorre; Кнорре В. Д.; A. A. Belogurov; Белогуров А. А.; N. A. Ponomarenko; Пономаренко Н. А.; S. M. Deyev; Деев С. М.; V. V. Vlasov; Власов В. В.; A. G. Gabibov; Габибов А. Г.

doi:10.32607/20758251-2014-6-4-54-59

Excessive Labeling Technique Provides a Highly Sensitive Fluorescent Probe for Real-time Monitoring of Biodegradation of Biopolymer Pharmaceuticals in vivo

Authors: Terekhov S.S.¹, Smirnov I.V.¹^,2, Shamborant O.G.¹, Zenkova M.A.³, Chernolovskaya E.L³, Gladkikh D.V.³, Murashev A.N.⁴, Dyachenko I.A.⁵, Knorre V.D.¹, Belogurov A.A.¹^,2^,6, Ponomarenko N.A.¹, Deyev S.M.¹, Vlasov V.V.³, Gabibov A.G.¹^,2^,6
Affiliations:
1. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
2. Kazan Federal University
3. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences
4. Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
5. Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino
6. Institute of Gene Biology, Russian Academy of Sciences
Issue: Vol 6, No 4 (2014)
Pages: 54-59
Section: Research Articles
Submitted: 17.01.2020
Published: 15.12.2014
URL: https://actanaturae.ru/2075-8251/article/view/10525
DOI: https://doi.org/10.32607/20758251-2014-6-4-54-59
ID: 10525

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Full Text

Abstract

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.

Keywords

fluorescent probe, biodegradation, pharmacokinetics, in vivo bioimaging, self-quenching, butyrylcholinesterase, proteolysis

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Excessive Labeling Technique Provides a Highly Sensitive Fluorescent Probe for Real-time Monitoring of Biodegradation of Biopolymer Pharmaceuticals in vivo

Full Text

Abstract

Keywords

About the authors

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

References

Supplementary files

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