Biomedical applications of copper-free click chemistry: in vitro, in vivo, and ex vivo

Kim, Eunha; Koo, Heebeom

doi:10.1039/c9sc03368h

Cited by 285 publications

(229 citation statements)

References 105 publications

Supporting

Mentioning

215

Contrasting

Unclassified

Order By: Relevance

“…Common types of click reactions include copper azide‐alkyne cycloadditions (CuAAC), strained promoted azide‐alkyne cycloadditions (SPAAC) and tetrazine ligation ( i.e. , inverse electron‐demand Diels–Alder, IEDDA) (44). Because copper may be toxic in vivo and lead to side reactions ( e.g .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Site‐specific Bioconjugation and Convergent Click Chemistry Enhances Antibody–Chromophore Conjugate Binding Efficiency

Sadiki

Kercher

et al. 2020

Photochem & Photobiology

View full text Add to dashboard Cite

Photosensitizer (PS)–antibody conjugates (photoimmunoconjugates, PICs) enable cancer cell‐targeted photodynamic therapy (PDT). Nonspecific chemical bioconjugation is widely used to synthesize PICs but gives rise to several shortcomings. The conjugates are heterogeneous, and the process is not easily reproducible. Moreover, modifications at or near the binding sites alter both binding affinity and specificity. To overcome these limitations, we introduce convergent assembly of PICs via a chemo‐enzymatic site‐specific approach. First, an antibody is conjugated to a clickable handle via site‐specific modification of glutamine (Gln) residues catalyzed by transglutaminase (TGase, EC 2.3.2.13). Second, the modified antibody intermediate is conjugated to a compatible chromophore via click chemistry. Utilizing cetuximab, we compared this site‐specific conjugation protocol to the nonspecific chemical acylation of amines using N‐hydroxysuccinimide (NHS) chemistry. Both the heavy and light chains were modified via the chemical route, whereas, only a glutamine 295 in the heavy chain was modified via chemo‐enzymatic conjugation. Furthermore, a 2.3‐fold increase in the number of bound antibodies per cell was observed for the site‐specific compared with nonspecific method, suggesting that multiple stochastic sites of modification perturb the antibody–antigen binding. Altogether, site‐specific bioconjugation leads to homogenous, reproducible and well‐defined PICs, conferring higher binding efficiency and probability of clinical success.

show abstract

Section: Introductionmentioning

confidence: 99%

“…Because copper may be toxic in vivo and lead to side reactions ( e.g . oxidation) (44), SPAAC and IEDDA are preferable alternatives. In order to utilize click reactions, compatible clickable handles need to be conjugated to antibody and as well as the PS.…”

Section: Introductionmentioning

confidence: 99%

Site‐specific Bioconjugation and Convergent Click Chemistry Enhances Antibody–Chromophore Conjugate Binding Efficiency

Sadiki

Kercher

et al. 2020

Photochem & Photobiology

View full text Add to dashboard Cite

show abstract

“…In addition, the biorthogonality of SPAAC allows the reaction to proceed in a complex biological environment. Therefore, SPAAC is one of the few reactions that can occur in vivo . However, there are only a few commercially available cyclooctyne derivatives on the market.…”

Section: Click Chemistry For Functionalization Of Reactive Particlesmentioning

confidence: 99%

“…Therefore, SPAAC is one of the few reactions that can occur in vivo. [87] However, there are only a few commercially available cyclooctyne derivatives on the market. In addition, similar to the CuAAC reaction, the functionalization with biomacromolecules requires the introduction of the cyclooctynes or azides prior to the conjugation.…”

Section: Complete Functionalization Using Spaacmentioning

confidence: 99%

Reactive Precursor Particles as Synthetic Platform for the Generation of Functional Nanoparticles, Nanogels, and Microgels

Gruber

Navarro

Klinger

2019

Adv Materials Inter

View full text Add to dashboard Cite

Precise control of the chemical functionality of polymer nanoparticles is a key requirement in tailoring their (dynamic) colloidal properties toward advanced applications. However, current synthetic techniques are still limited in the versatility of chemical design and preparation of such functional colloidal nanomaterials. Two major challenges remain: First, various particle preparation methods are restricted in their functional group tolerance, thus hindering certain combinations of polymer backbones with specific functional groups. Second, the preparation of particles with different functionalities requires the synthesis of different particle batches. But this often results in a simultaneous variation of colloidal features. As a result, the accurate determination of important structure–property relations is still hindered. To address these restrictions, postmodification of preformed reactive particles is gaining more attention. This technique has evolved from polymer synthesis, where postpolymerization functionalization enables the introduction of a plethora of functional groups without changing the degree of polymerization and the molecular weight distribution. Similarly, modifying precursor particles enables the introduction of functional groups into particles while reducing variations in colloidal features, e.g., particle size and size distribution. This powerful synthetic method complements established procedures for functionalization of particle surfaces, thereby enabling the facile preparation of (multi‐)functional particle libraries, which will allow precise investigations of structure–property relations.

show abstract

“…[12][13][14] The development of bioorthogonal reactions to expand the bioorthogonal tool box has been of intense research interest. [15][16][17][18] However, it remains a great challenge to establish new bioorthogonal reactions that are orthogonal to the most commonly used bioorthogonal reactions such as azide alkyne cycloaddition (AAC) catalysed by Cu (CuAAC) or promoted by strain (SPAAC). 19,20 Inverse electron-demand Diels-Alder cycloaddition (IEDDAC) reactions using various strained alkenes have been established as new bioorthogonal tools that are orthogonal to current AAC chemistry.…”

Section: Introductionmentioning

confidence: 99%

Photo-controllable bioorthogonal chemistry for spatiotemporal control of bio-targets in living systems

Kong

Zhu

et al. 2020

Chem. Sci.

View full text Add to dashboard Cite

The establishment of bioorthogonal chemistry is one of the most significant advances in chemical biology using exogenous chemistry to perturb and study biological processes. Photo-modulation of biological systems has realized temporal and spatial control on biomacromolecules in living systems. The combination of photo-modulation and bioorthogonal chemistry is therefore emerging as a new direction to develop new chemical biological tools with spatiotemporal resolution. This minireview will focus on recent development of bioorthogonal chemistry subject to spatiotemporal control through photo-irradiation. Different strategies to realize photo-control on bioorthogonal bond-forming reactions and biological applications of photo-controllable bioorthogonal reactions will be summarized to give a perspective on how the innovations on photo-chemistry can contribute to the development of optochemical biology. Future trends to develop more optochemical tools based on novel photochemistry will also be discussed to envision the development of chemistry-oriented optochemical biology.

show abstract

Biomedical applications of copper-free click chemistry: in vitro, in vivo, and ex vivo

Abstract: Copper-free click chemistry has resulted in a change of paradigm, showing that artificial chemical reactions can occur on cell surfaces, in cell cytosol, or within the body. It has emerged as a valuable tool in biomedical fields.

Cited by 285 publications

References 105 publications

Site‐specific Bioconjugation and Convergent Click Chemistry Enhances Antibody–Chromophore Conjugate Binding Efficiency

Site‐specific Bioconjugation and Convergent Click Chemistry Enhances Antibody–Chromophore Conjugate Binding Efficiency

Reactive Precursor Particles as Synthetic Platform for the Generation of Functional Nanoparticles, Nanogels, and Microgels

Photo-controllable bioorthogonal chemistry for spatiotemporal control of bio-targets in living systems

Contact Info

Product

Resources

About