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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
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Affiliations:
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
- Kazan Federal University
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences
- Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
- Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino
- Institute of Gene Biology, Russian Academy of Sciences
- Issue: Vol 6, No 4 (2014)
- Pages: 54-59
- Section: Research Articles
- 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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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.
About the authors
S. S. Terekhov
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
Author for correspondence.
Email: sterekhoff@mail.ru
Russian Federation
I. V. Smirnov
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences; Kazan Federal University
Email: sterekhoff@mail.ru
Russian Federation
O. G. Shamborant
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
Email: sterekhoff@mail.ru
Russian Federation
M. A. Zenkova
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences
Email: sterekhoff@mail.ru
Russian Federation
E. L Chernolovskaya
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences
Email: sterekhoff@mail.ru
Russian Federation
D. V. Gladkikh
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences
Email: sterekhoff@mail.ru
Russian Federation
A. N. Murashev
Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
Email: sterekhoff@mail.ru
Russian Federation
I. A. Dyachenko
Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino
Email: sterekhoff@mail.ru
Russian Federation
V. D. Knorre
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
Email: sterekhoff@mail.ru
Russian Federation
A. A. Belogurov
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences; Kazan Federal University; Institute of Gene Biology, Russian Academy of Sciences
Email: sterekhoff@mail.ru
Russian Federation
N. A. Ponomarenko
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
Email: sterekhoff@mail.ru
Russian Federation
S. M. Deyev
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
Email: sterekhoff@mail.ru
Russian Federation
V. V. Vlasov
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences
Email: sterekhoff@mail.ru
Russian Federation
A. G. Gabibov
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences; Kazan Federal University; Institute of Gene Biology, Russian Academy of Sciences
Email: sterekhoff@mail.ru
Russian Federation
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