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. 2019 Aug 16;10(34):7835–7851. doi: 10.1039/c9sc03368h

Table 2. Summary of the copper-free click chemistry research for biomedical applications.

Location Application Click molecules used Type
In vitro PARP1 imaging35 AZD2281-TCO/Tz-Texas Red iEDDA
PARP1 target identification study36 AZD2281-TCO/Tz-cleavable linker-biotin iEDDA
Tubulin protein imaging37 Taxol-TCO/Tz-BODIPY FL iEDDA
Polo-like kinase 1 protein imaging38 BI2536-TCO/Tz-Texas Red iEDDA
Aurora kinase A protein imaging39 MLN8054-TCO/Tz-CFDA, Tz-Texas Red iEDDA
MET protein imaging40 PF04217903-TCO/Tz-CFDA iEDDA
Foretinib-TCO/Tz-CFDA iEDDA
Imaging binding targets of drug molecules41 Dasatinib-TCO/Tz-CFDA iEDDA
BTK protein imaging42 Ibrutinib-TCO/Tz-Cy5 iEDDA, SPACC
Ibrutinib-N3/DBCO-Cy5
Drug imaging43 JQ1-TCO/Tz-Cy5 iEDDA
Visualization of PTM modification44 NAD+-DBCO/N3-Cy3, N3-Cy5 SPACC
NAD+-methyl cyclopropene/Tz-Cy3 iEDDA
Site-specific oligonucleotide labelling4547 RNA-norbornene/Tz-Oregon Green 488 iEDDA
RNA-methyl cyclopropene/Tz-Oregon Green 488
DNA-Tz/BCN-rhodamine
DNA-methyl cyclopropene/Tz-BODIPY
Site-specific protein labelling48 l-Lysine-TCO/Tz-Cy5 iEDDA
No-wash STED imaging49 Phalloidin-BCN/Tz-Cy3 iEDDA
In vivo Zebrafish embryo growth imaging24 N-Acetylgalactosamine (GalNAc)/difluorinated cyclooctyne (DIFO)-Alexa Fluor dye SPACC
Glycan imaging by intraperitoneal injection50 Tetraacetylated N-azidoacetyl-d-mannosamine (Ac4ManNAz)/DIFO-FLAG peptide conjugate SPACC
Brain glycan imaging51 Liposomes loading 9-azido sialic acid/DBCO-Cy5.5 SPACC
Tumor glycan imaging by SPECT52 Anti-TAG72 antibody CC49-TCO/Tz-111In SPACC
Tumor glycan imaging by MR53 Ac4GalNAz/TMDIBO-Lys-Gd (tetramethoxydibenzocyclooctyne-lysine-gadolinium) SPACC
Tumor VEGF (vascular endothelial growth factor receptor 2) imaging by ultrasound54 Antivascular endothelial growth factor receptor 2 antibody (TCO-antiVEGFR2)/Tz-modified microbubbles iEDDA
Acute thrombus imaging by ultrasound55 AntiCD62p-TCO/Tz-modified microbubbles iEDDA
Tumor-targeted liposomes for drug delivery25 Ac4ManNAz/DBCO-modified liposome SPACC
Tumor-targeted photosensitizer delivery27 Ac4ManNAz-loading chitosan nanoparticles/DBCO-modified chitosan nanoparticles SPACC
Tumor-targeted doxorubicin delivery56 Peptide-modified Ac4ManNAz/DBCO-modified doxorubicin SPACC
Upconversion nanoparticle-based photodynamic therapy57 Upconversion NP modified with Tz groups/norborane (NB)-conjugated rose bengal (RB) iEDDA
Endothelial progenitor cell therapy for myocardiac infarction58 Azide-modified CD34 antibody/DBCO-modified CD41 antibody SPACC
Ex vivo Glycoproteomic analysis of intact and hypertrophy hearts59 Ac4ManNAz/DBCO-Fluor 488 SPACC
Analysis of microvesicles from the blood of glioblastomas patients60 Antibody-modified TCO/Tz-modified magnetic nanoparticles iEDDA
Amplification of signal for diagnosis purpose61 Antibody-modified TCO/Tz-modified magneto-fluorescent nanoparticles iEDDA
Study of protein dynamics in the neuronal system62 Azidohomoalanine/DIFO-biotin SPACC
Study of the conformational change of protein by FRET63 Unnatural amino acid containing tetrazine or norbornene/BODIPY-FL tetrazine or BODIPY-TMR-X bicyclononyne iEDDA, SPACC
Nucleotide ligation for the CRISPR Cas9 system64 RNAs modified with alkyne or DBCO/RNAs modified with azide CuAAC, SPACC