Protein modification by thiolactone homocysteine chemistry: a multifunctionalized human serum albumin theranostic

Popova, Tatyana V.; Krumkacheva, Olesya A.; Burmakova, Anna S.; Spitsyna, Anna; Zakharova, Olga D.; Lisitskiy, Vladimir A.; Kirilyuk, Igor A.; Silnikov, Vladimir N.; Bowman, Michael K.; Bagryanskaya, Elena G.; Godovikova, Tatyana S.

doi:10.1039/c9md00516a

Cited by 5 publications

(5 citation statements)

References 88 publications

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“…HTL is a quite beneficial synthetic block for preparing different multifunctional agents [ 11 , 12 , 13 , 14 , 15 , 60 , 61 ]. HTL is susceptible to both nucleophilic and electrophilic attack because of its dual aminoacyl-thioester character.…”

Section: Resultsmentioning

confidence: 99%

“…Due to continuous blood circulation and low immunological effect, human serum albumin (HSA) is successfully used as a core to improve the potential of therapeutic agents in theranostic constructions [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. The efficiency of HSA as a carrier of cytostatics has been proven [ 16 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

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Human Serum Albumin Labelling with a New BODIPY Dye Having a Large Stokes Shift

Raskolupova

Popova²,

Zakharova

et al. 2021

Molecules

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BODIPY dyes are photostable neutral derivatives of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene. These are widely used as chemosensors, laser materials, and molecular probes. At the same time, BODIPY dyes have small or moderate Stokes shifts like most other fluorophores. Large Stokes shifts are preferred for fluorophores because of higher sensitivity of such probes and sensors. The new boron containing BODIPY dye was designed and synthesized. We succeeded to perform an annulation of pyrrole ring with coumarin heterocyclic system and achieved a remarkable difference in absorption and emission maximum of obtained fluorophore up to 100 nm. This BODIPY dye was equipped with linker arm and was functionalized with a maleimide residue specifically reactive towards thiol groups of proteins. BODIPY residue equipped with a suitable targeting protein core can be used as a suitable imaging probe and agent for Boron Neutron Capture Therapy (BNCT). As the most abundant protein with a variety of physiological functions, human serum albumin (HSA) has been used extensively for the delivery and improvement of therapeutic molecules. Thiolactone chemistry provides a powerful tool to prepare albumin-based multimodal constructions. The released sulfhydryl groups of the homocysteine functional handle in thiolactone modified HSA were labeled with BODIPY dye to prepare a labeled albumin-BODIPY dye conjugate confirmed by MALDI-TOF-MS, UV-vis, and fluorescent emission spectra. Cytotoxicity of the resulting conjugate was investigated. This study is the basis for a novel BODIPY dye-albumin theranostic for BNCT. The results provide further impetus to develop derivatives of HSA for delivery of boron to cancer cells.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Human Serum Albumin Labelling with a New BODIPY Dye Having a Large Stokes Shift

Raskolupova

Popova²,

Zakharova

et al. 2021

Molecules

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“…Due to continuous blood circulation and low immunological effect HSA is successfully used as a core to improve the potential of therapeutic agents [12][13][14][15][16][17][18][19]. The binding of BODIPY residues to proteins is a rather recent topic for research.…”

Section: Bioconjugationmentioning

confidence: 99%

“…Homocysteine thiolactone (HTL) is a quite valuable synthetic building block to prepare different multifunctional agents [16][17][18][19]26,27]. Because of its dual aminoacyl-thioester character, homocysteine thiolactone is susceptible to both nucleophilic and electrophilic attack.…”

Section: Bioconjugationmentioning

confidence: 99%

New BODIPY Dye with a Large Stokes Shift for Biopolymer Labelling

Raskolupova

Popova

Zakharova

et al. 2020

The 24th International Electronic Conference on Synthetic Organic Chemistry

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As the most abundant protein with a variety of physiological functions, human serum albumin (HSA) has been used extensively for the delivery and improvement of therapeutic molecules. Thiolactone chemistry provides a powerful tool to prepare albumin-based multimodal imaging probes and agents for Boron Neutron Capture Therapy (BNCT). For this purpose, boron containing BODIPY dye was designed and synthesized. BODIPY dyes are photostable neutral derivatives of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene. These are widely used as chemosensors, laser materials and molecular probes. In the same time, BODIPY dyes as most other fluorophores have small or moderate Stokes shifts. Large Stokes shifts are preferred for fluorophores because of higher sensitivity of such probes and sensors. We succeeded to perform an annulation of pyrrole ring with coumarin heterocyclic system and achieved a remarkable difference in absorption and emission maximum of obtained fluorophore up to 100 nm. Moreover, this BODIPY dye was equipped with linker arm and was functionalized with a maleimide residue specifically reactive towards thiol groups of proteins. The released sulfhydryl groups of the homocysteine functional handle in thiolactone modified HSA was labeled with BODIPY dye to prepare a labeled albumin-BODIPY dye conjugate confirmed by MALDI-TOF-MS, UV-vis and fluorescent emission spectra. The cytotoxicity of HSA conjugate was evaluated by MTT assay in cell lines MCF-7 and T98G. This is the basis for a novel BODIPY dye-albumin theranostic for BNCT. These results provide further impetus to develop derivatives of HSA for delivery of Boron to cancer cells.

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“…Previously, we reported on the synthesis of fluorophore-labeled homocystamide conjugates of human serum albumin and their use in thiol-‘click’ chemistry [ 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. Furthermore, we reported on the preparation of the novel multimodal boronated albumin-based theranostic agents, which could be accumulated in tumor cells [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

Design of the New Closo-Dodecarborate-Containing Gemcitabine Analogue for the Albumin-Based Theranostics Composition

et al. 2023

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Combination therapy is becoming an increasingly important treatment strategy because multi-drugs can maximize therapeutic effect and overcome potential mechanisms of drug resistance. A new albumin-based theranostic containing gemcitabine closo-dodecaborate analogue has been developed for combining boron neutron capture therapy (BNCT) and chemotheraphy. An exo-heterocyclic amino group of gemcitabine was used to introduce closo-dodecaborate, and a 5′-hydroxy group was used to tether maleimide moiety through an acid-labile phosphamide linker. The N-trifluoroacylated homocysteine thiolactone was used to attach the gemcitabine analogue to human serum albumin (HSA) bearing Cy5 or Cy7 fluorescent dyes. The half-maximal inhibitory concentration (IC50) of the designed theranostic relative to T98G cells was 0.47 mM with the correlation coefficient R = 0.82. BNCT experiments resulted in a decrease in the viability of T98G cells, and the survival fraction was ≈ 0.4.

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Protein modification by thiolactone homocysteine chemistry: a multifunctionalized human serum albumin theranostic

Abstract: As the most abundant protein with a variety of physiological functions, albumin has been used extensively for the delivery of therapeutic molecules. Thiolactone chemistry provides a powerful tool to prepare...

Cited by 5 publications

References 88 publications

Human Serum Albumin Labelling with a New BODIPY Dye Having a Large Stokes Shift

Human Serum Albumin Labelling with a New BODIPY Dye Having a Large Stokes Shift

New BODIPY Dye with a Large Stokes Shift for Biopolymer Labelling

Design of the New Closo-Dodecarborate-Containing Gemcitabine Analogue for the Albumin-Based Theranostics Composition

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