Speaker
Mrs
Tatyana Avramchuk
(Institute of Chemical Biology and Fundamental Medicine)
Description
Development of boron nanocarriers as theranostic agents for boron neutron capture therapy has received extensive attention in recent years. Different albumin conjugates have proved over the years to be highly biocompatible, with some of them being FDA approved and currently used in clinical treatments. However, the chemistry for site-directed introduced boron into human serum albumin is quite limited. Only maleimide-functionalized close-dodecaborate was coupled to the single and surface-exposed cysteine-34 residue of albumin via a Michael addition reaction.1 Novel strategies site-directed labeling of the protein by boron reagents that are directly applicable to native proteins, that avoid the need for genetic engineering, and that do not rely on the relatively rare free sulfhydral group of cysteine remain highly desirable. A novel albumin-based boron delivery nanoplatform was developed in this research by simple conjugation of undecahydro-closo-dodecaborate to multimodal albumin homocystamides. A dual-labeled albumin-based molecular probe for 19F MRI and fluorescence microscopy has been obtained by functionalizing the protein with maleimide of a fluorescent dye and a fluorinated thiolactone derivative. The procedure of boron labeling has involved modifying the released sulfhydryl group of a homocysteine functional handle in the albumin structure by an undecahydro-closo-dodecaborate reagent. The successful preparation of boron-containing albumins were confirmed by MALDI-TOF-MS, inductively coupled plasma atomic emission spectroscopy, UV-Vis and fluorescent emission spectra.
The work is supported by Russian Scientific Foundation grant 19-74-20123.
1. Nakamura, H., Kikuchi, S., Kawai, K., Ishii, S., and Sato, S. (2018) closo-Dodecaborate-conjugated human serum albumins: preparation and in vivo selective boron delivery to tumor. Pure Appl. Chem. 90, 745–753.
Summary
A novel albumin-based boron delivery nanoplatform was developed in this research by simple conjugation of undecahydro-closo-dodecaborate to multimodal albumin homocystamides. A dual-labeled albumin-based molecular probe for 19F MRI and fluorescence microscopy has been obtained by functionalizing the protein with maleimide of a fluorescent dye and a fluorinated thiolactone derivative.The successful preparation of boron-containing albumins were confirmed by MALDI-TOF-MS, inductively coupled plasma atomic emission spectroscopy, UV-Vis and fluorescent emission spectra.
Primary author
Mrs
Tatyana Avramchuk
(Institute of Chemical Biology and Fundamental Medicine)
Co-authors
Mr
Georgii Panasenko
(Institute of Chemical Biology and Fundamental Medicine)
Dr
Ludmila Koroleva
(Institute of Chemical Biology and Fundamental Medicine)
Dr
Olga Zakharova
(Institute of Chemical Biology and Fundamental Medicine)
Prof.
Sergey Taskaev
(Budker Institute of Nuclear Physics)
Dr
Tatyana Godovikova
(Institute of Chemical Biology and Fundamental Medicine)
Mr
Vladimir Lisitskiy
(Institute of Chemical Biology and Fundamental Medicine)
Prof.
Vladimir Silnikov
(Institute chemical biology and fundamental medicine)
