TY - JOUR

T1 - Preparation of Boron-Containing S-Nitrosothiol Based on Homocysteinylamides of Human Serum Albumin for Combined NO-Chemical and Boron-Neutron-Capture Therapy

AU - Popova, T. V.

AU - Van, M.

AU - Kurochkin, T. N.

AU - Tsyrempilov, S. A.

AU - Zakharova, O. D.

AU - Silnikov, V. N.

AU - Godovikova, T. S.

N1 - The study was supported by the state assignment of the Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of Sciences no. 121031300042-1. Preparation of Boron-Containing S-Nitrosothiol Based on Homocysteinylamides of Human Serum Albumin for Combined NO-Chemical and Boron-Neutron-Capture Therapy / T. V. Popova, M. Van, T. N. Kurochkin [et al.] // Russian Journal of Bioorganic Chemistry. – 2025. – Vol. 51, No. 1. – P. 202-215. – DOI 10.1134/S1068162025010194.

PY - 2025/2/12

Y1 - 2025/2/12

N2 - Abstract: Objective: The strategic aim of this work is to create a fluorophore-labelled, clinically relevant exogenous NO donor carrying a boron-containing compound residue based on human serum albumin (HSA) for the implementation of combined NO-chemotherapy and boron-neutron-capture therapy. Methods: By selective modification of the Cys34 residue of albumin with a maleimide derivative of a fluorescent dye and subsequent N-homocysteinylation with a thiolactone derivative of homocysteine containing a clozo-dodecaborate residue, a nanoconstruct for boron-neutron-capture therapy was obtained. An analogue based on the natural modifier, boron-containing homocysteine thiolactone, was synthesised by alkylation of the amino group of thiolactone with a dioxonium derivative of clozo-dodecaborate. Post-synthetic modification of the lysine residues of the protein using the boron thiolactone of homocysteine provided the introduction of SH groups into the protein and the possibility of subsequent trans-S-nitrosylation of the protein using S-nitrosoglutathione. Results and Discussion: It was found that 2 M of NO was conjugated to 1 M of boron-containing HSA. Boron-containing S-nitrosothiol based on albumin homocysteinylamide, without epithermal neutron irradiation, was demonstrated to be more cytotoxic against human glioblastoma cell lines than the boron-containing albumin conjugate. Conclusions: Thus, the approach used allows obtaining a boron-enriched structure based on a biocompatible tumor-specific protein, containing a fluorescent label and an increased number of S-nitroso groups. It is necessary for the manifestation of a chemotherapeutic effect of the construct. The practical significance of this structure lies in the possibility of a cancer treatment, combining chemo- and boron-neutron capture therapy.

AB - Abstract: Objective: The strategic aim of this work is to create a fluorophore-labelled, clinically relevant exogenous NO donor carrying a boron-containing compound residue based on human serum albumin (HSA) for the implementation of combined NO-chemotherapy and boron-neutron-capture therapy. Methods: By selective modification of the Cys34 residue of albumin with a maleimide derivative of a fluorescent dye and subsequent N-homocysteinylation with a thiolactone derivative of homocysteine containing a clozo-dodecaborate residue, a nanoconstruct for boron-neutron-capture therapy was obtained. An analogue based on the natural modifier, boron-containing homocysteine thiolactone, was synthesised by alkylation of the amino group of thiolactone with a dioxonium derivative of clozo-dodecaborate. Post-synthetic modification of the lysine residues of the protein using the boron thiolactone of homocysteine provided the introduction of SH groups into the protein and the possibility of subsequent trans-S-nitrosylation of the protein using S-nitrosoglutathione. Results and Discussion: It was found that 2 M of NO was conjugated to 1 M of boron-containing HSA. Boron-containing S-nitrosothiol based on albumin homocysteinylamide, without epithermal neutron irradiation, was demonstrated to be more cytotoxic against human glioblastoma cell lines than the boron-containing albumin conjugate. Conclusions: Thus, the approach used allows obtaining a boron-enriched structure based on a biocompatible tumor-specific protein, containing a fluorescent label and an increased number of S-nitroso groups. It is necessary for the manifestation of a chemotherapeutic effect of the construct. The practical significance of this structure lies in the possibility of a cancer treatment, combining chemo- and boron-neutron capture therapy.

KW - S-nitrosoglutathione

KW - S-nitrosylated boron-containing albumin homocysteinamide

KW - boron neutron capture therapy

KW - boron-containing homocysteine thiolactone

KW - closo-dodecaborate

UR - https://www.mendeley.com/catalogue/18c023c1-2e63-3d8b-8fd3-4fb598b9c184/

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85218826652&origin=inward&txGid=7e3ccfad50f6a4490ec13c6260b9fc91

UR - https://elibrary.ru/item.asp?id=80320830

U2 - 10.1134/S1068162025010194

DO - 10.1134/S1068162025010194

M3 - Article

VL - 51

SP - 202

EP - 215

JO - Russian Journal of Bioorganic Chemistry

JF - Russian Journal of Bioorganic Chemistry

SN - 1068-1620

IS - 1

ER -