Antibody dual-functionalisation enabled through a modular divinylpyrimidine disulfide rebridging strategy

Hanby, Abigail R.; Walsh, Stephen J.; Counsell, Andrew J.; Ashman, Nicola; Mortensen, Kim T.; Carroll, Jason S.; Spring, David R.

doi:10.1039/d2cc02515a

Cited by 9 publications

(5 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…174 3-Bromo-5-methylene pyrrolones 49 and dibromopyridazinedione derivatives ( 143a ) 192,193 follow a similar route. On the other hand, 1,3-dihaloacetone or dichloroacetophenone derivatives ( 144a ), 376–378 dibromomethylquinoxaline ( 145a ), 375,379 divinylpyrimidines ( 146a ), 201,380 divinyltriazines ( 147a ), 202 diethynyl phosphinate ( 148a ), 207,381 bis-ethynylphosphonamidate ( 149a ), 382 dibromomaleimide, 184,311,383 3,4-dithiophenoylmaleimide ( 150a ), 384 arylene dipropiolonitrile ( 151a , Fig. 35) 210 phenyldivinylsulfonamides ( 152a ), 385 2-chloro-2-phenylethanethioester ( 153a ), 386 oxSTEF reagents ( 154a ), 387 3-bromo-5-methylene pyrrolones ( 12a ), 49 and DiPODS ( 156a , two oxadiazolyl methyl sulfones connected by a phenyl group) were also used for synthesis of disulfide-targeted antibody conjugates ( 156b ).…”

Section: Meeting Technological Demands At the Biology–medicine Interfacementioning

confidence: 99%

Chemical technology principles for selective bioconjugation of proteins and antibodies

Chauhan,

V.,

Kumar

et al. 2024

Chem. Soc. Rev.

View full text Add to dashboard Cite

show abstract

Section: Meeting Technological Demands At the Biology–medicine Interfacementioning

confidence: 99%

Chemical technology principles for selective bioconjugation of proteins and antibodies

Chauhan,

V.,

Kumar

et al. 2024

Chem. Soc. Rev.

View full text Add to dashboard Cite

show abstract

“…Alkynes have also been employed for rebridging via thiol–yne coupling or via their incorporation in diethynyl phosphinates . Other examples of rebridging reagents include organic arsenicals, divinylpyrimidines, − arylene dipropiolonitriles (ADPN), di(bromomethyl)pyridines, diPODS, or oxSTEF reagents …”

Section: Introductionmentioning

confidence: 99%

Fluorine-18 and Radiometal Labeling of Biomolecules via Disulfide Rebridging

Richard,

Martin Aubert,

Denis

et al. 2023

Bioconjugate Chem.

View full text Add to dashboard Cite

Biomolecules labeled with positron-emitting radionuclides like fluorine-18 or radiometals like copper-64 and zirconium-89 are increasingly employed in nuclear medicine for diagnosis purposes. Given the fragility and complexity of these compounds, their labeling requires mild conditions. Besides, it is essential to develop methods inducing minimal modification of the tertiary structure, as it is fundamental for the biological activity of such complex entities. Given these requirements, disulfide rebridging represents a promising possibility since it allows protein modification as well as conservation of the tertiary structure. In this context, we have developed an original radiofluorinated dibromopyridazine dione prosthetic group for labeling of disulfide-containing biomolecules via rebridging. We employed it to radiolabel octreotide, a somatostatin analogue, and to radiolabel fragment antigen binding (Fab) targeting programmed death-ligand 1 (PD-L1), whose properties were then evaluated in vitro and in vivo by positron emission tomography (PET) imaging. We next extended our strategy to the radiolabeling of cetuximab, a monoclonal antibody, with various radiometals commonly used in PET imaging (zirconium-89, copper-64) by developing various rebridging molecules bearing the appropriate chelators. The stabilities of the radiolabeled antibody conjugates were assessed in biological conditions.

show abstract

“…In this study (Scheme ), the in situ-synthesized ZnGa 2 O 4 :Cr 3+ (ZGC) nanoparticles were embedded in the mesoporous silica nanoshell-coated gold nanorods (GNR@MSNs) to give the nanocomposites of cGNR@MSNs, − which provided the light-emitting element for PL imaging. − Additionally, the nanocomposites of cGNR@MSNs acted as drug delivery vehicles for camptothecin (CPT) and covalently captured anti-CD40 antibodies as a nanogate to control the release behaviors of entrapped drugs. , The anti-CD40 nanogate was constructed by attaching the divinylpyrimidine (DVP) groups on the surface of cGNR@MSNs, which selectively conjugated with anti-CD40 and re-bridged disulfide bonds of antibodies. − The novel anti-CD40-gated cGNR@MSNs simultaneously delivered chemotherapy drugs of CPT and immunotherapy drugs of anti-CD40, boosting the tumor inhibitory effect for cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

Multi-Armed Anti-CD40-Mediated Dual Drug Delivery System Based on Mesoporous Silica/Au Nanorod Nanocomposites for Multimodality Imaging and Combination Therapy

Feng

Zhao

et al. 2023

ACS Appl. Nano Mater.

View full text Add to dashboard Cite

Nanotechnology provides the platform to develop functional nanocomposites with outstanding features, such as persistent luminescence (PL), photothermal conversion, magnetic resonance (MR), and so on, that has been incorporated in nanomedicine for diagnosis and therapy. Herein, the nanocomposites of ZnGa 2 O 4 :Cr 3+ embedded in mesoporous silica coating surrounding gold nanorods (cGNR@MSNs) were developed for the codelivery of chemotherapeutic drugs and anti-CD40 antibodies. The nanocomposites were functionalized with tetrazaheterocycle linking divinylpyrimidine derivatives (DOTVs), which covalently capture anti-CD40 by disulfide re-bridging on the surface of cGNR@MSNs. The anti-CD40-mediated dual drug delivery system simultaneously realized the combination of chemo-, immuno-, and photothermal therapies, enhancing the synergistic effect of combination therapy for multiple tumor cells. Moreover, the nanodrug delivery system achieved multimodality imaging with fluorescence, PL, and MR modes for precise diagnosis. This study provides fascinating insights into the development of nanocomposite-based multimodality imaging strategies and imagingguided combination therapies.

show abstract

Antibody dual-functionalisation enabled through a modular divinylpyrimidine disulfide rebridging strategy

Abstract: Herein we report the development of a methodology for the dual-functionalisation of IgG antibodies. This is accomplished through the combination of disulfide rebridging divinylpyrimidine technology, with bicyclononyne and methylcyclopropene handles...

Cited by 9 publications

References 24 publications

Chemical technology principles for selective bioconjugation of proteins and antibodies

Chemical technology principles for selective bioconjugation of proteins and antibodies

Fluorine-18 and Radiometal Labeling of Biomolecules via Disulfide Rebridging

Multi-Armed Anti-CD40-Mediated Dual Drug Delivery System Based on Mesoporous Silica/Au Nanorod Nanocomposites for Multimodality Imaging and Combination Therapy

Contact Info

Product

Resources

About