Login Register Cart 0
Generic placeholder image

Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Current Frontiers

Applications of Bioorthogonal Chemistry in Tumor-Targeted Drug Discovery

Author(s): Gang Liu, Eric A. Wold and Jia Zhou*

Volume 19, Issue 11, 2019

Page: [892 - 897] Pages: 6

DOI: 10.2174/1568026619666190510091921

Abstract

Chemical reactions that can proceed in living systems while not interfering with native biochemical processes are collectively referred to as bioorthogonal chemistry. Selectivity, efficiency, and aqueous compatibility are three significant characteristics of an ideal bioorthogonal reaction. To date, the specialized bioorthogonal reactions that have been reported include: Cu (I)-catalyzed [3 + 2] azido– alkyne cycloadditions (CuAAC), strain-promoted [3 + 2] azide–alkyne cycloadditions (SPAAC), Staudinger ligation, photo-click 1,3-dipolar cycloadditions, strain-promoted alkyne-nitrone cycloadditions (SPANC), transition metal catalysis (TMC), and inverse electron demand Diels–Alder (IEDDA). These reactions are divided into two subtypes, 1) bond-formation reactions (e.g. CuAAC, SPAAC, photo-click cycloadditions, SPANC), which can be conventionally applied in the chemical biology field for target identification, protein-specific modifications and others; and 2) bond-release reactions (e.g. Staudinger ligation, TMC, and IEDDA), which are emerging as powerful approaches for the study of protein activation and drug discovery. Over the past decade, bioorthogonal chemistry has enabled important compound design features in targeted drug discovery and has expanded biological knowledge on intractable targets. Research groups have also focused on the discovery of reactions with improved biocompatibility and increased reaction rates, which will undoubtably prove essential for future therapeutic development. Herein, we highlight two significant applications of bioorthogonal chemistry to drug discovery, which are tumor-targeted prodrug delivery and activation, and self-assembly of bifunctional molecules. The relevant challenges and opportunities are also discussed.

Keywords: Chemical reactions, Bioorthogonal Chemistry, Tumor-targeted drug discovery, Bifunctional molecules, Protein activation.

« Previous Next »
[1]
Oliveira, B.L.; Guo, Z.; Bernardes, G.J.L. Inverse electron demand Diels-Alder reactions in chemical biology. Chem. Soc. Rev., 2017, 46(16), 4895-4950. [http://dx.doi.org/10.1039/C7CS00184C]. [PMID: 28660957].
[2]
Azoulay, M.; Tuffin, G.; Sallem, W.; Florent, J.C. A new drug-release method using the Staudinger ligation. Bioorg. Med. Chem. Lett., 2006, 16(12), 3147-3149. [http://dx.doi.org/10.1016/j.bmcl.2006.03.073]. [PMID: 16621529].
[3]
van Brakel, R.; Vulders, R.C.M.; Bokdam, R.J.; Grüll, H.; Robillard, M.S. A doxorubicin prodrug activated by the staudinger reaction. Bioconjug. Chem., 2008, 19(3), 714-718. [http://dx.doi.org/10.1021/bc700394s]. [PMID: 18271515].
[4]
Mahato, R.; Tai, W.; Cheng, K. Prodrugs for improving tumor targetability and efficiency. Adv. Drug Deliv. Rev., 2011, 63(8), 659-670. [http://dx.doi.org/10.1016/j.addr.2011.02.002]. [PMID: 21333700].
[5]
Srinivasarao, M.; Low, P.S. Ligand-targeted drug delivery. Chem. Rev., 2017, 117(19), 12133-12164. [http://dx.doi.org/10.1021/acs.chemrev.7b00013]. [PMID: 28898067].
[6]
Matikonda, S.S.; Orsi, D.L.; Staudacher, V.; Jenkins, I.A.; Fiedler, F.; Chen, J.; Gamble, A.B. Bioorthogonal prodrug activation driven by a strain-promoted 1,3-dipolar cycloaddition. Chem. Sci. (Camb.), 2015, 6(2), 1212-1218. [http://dx.doi.org/10.1039/C4SC02574A]. [PMID: 29560207].
[7]
Versteegen, R.M.; Rossin, R.; ten Hoeve, W.; Janssen, H.M.; Robillard, M.S. Click to release: Instantaneous doxorubicin elimination upon tetrazine ligation. Angew. Chem. Int. Ed. Engl., 2013, 52(52), 14112-14116. [http://dx.doi.org/10.1002/anie.201305969]. [PMID: 24281986].
[8]
Rossin, R.; van Duijnhoven, S.M.; Ten Hoeve, W.; Janssen, H.M.; Kleijn, L.H.; Hoeben, F.J.; Versteegen, R.M.; Robillard, M.S. Triggered drug release from an antibody-drug conjugate using fast “click-to-release” chemistry in mice. Bioconjug. Chem., 2016, 27(7), 1697-1706. [http://dx.doi.org/10.1021/acs.bioconjchem.6b00231]. [PMID: 27306828].
[9]
Rossin, R.; Versteegen, R.M.; Wu, J.; Khasanov, A.; Wessels, H.J.; Steenbergen, E.J.; Ten Hoeve, W.; Janssen, H.M.; van Onzen, A.H.A.M.; Hudson, P.J.; Robillard, M.S. Chemically triggered drug release from an antibody-drug conjugate leads to potent antitumour activity in mice. Nat. Commun., 2018, 9(1), 1484. [http://dx.doi.org/10.1038/s41467-018-03880-y]. [PMID: 29728559].
[10]
Yao, Q.; Lin, F.; Fan, X.; Wang, Y.; Liu, Y.; Liu, Z.; Jiang, X.; Chen, P.R.; Gao, Y. Synergistic enzymatic and bioorthogonal reactions for selective prodrug activation in living systems. Nat. Commun., 2018, 9(1), 5032. [http://dx.doi.org/10.1038/s41467-018-07490-6]. [PMID: 30487642].
[11]
Weiss, J.T.; Dawson, J.C.; Fraser, C.; Rybski, W.; Torres-Sánchez, C.; Bradley, M.; Patton, E.E.; Carragher, N.O.; Unciti-Broceta, A. Development and bioorthogonal activation of palladium-labile prodrugs of gemcitabine. J. Med. Chem., 2014, 57(12), 5395-5404. [http://dx.doi.org/10.1021/jm500531z]. [PMID: 24867590].
[12]
Weiss, J.T.; Dawson, J.C.; Macleod, K.G.; Rybski, W.; Fraser, C.; Torres-Sánchez, C.; Patton, E.E.; Bradley, M.; Carragher, N.O.; Unciti-Broceta, A. Extracellular palladium-catalysed dealkylation of 5-fluoro-1-propargyl-uracil as a bioorthogonally activated prodrug approach. Nat. Commun., 2014, 5, 3277. [http://dx.doi.org/10.1038/ncomms4277]. [PMID: 24522696].
[13]
Pérez-López, A.M.; Rubio-Ruiz, B.; Sebastián, V.; Hamilton, L.; Adam, C.; Bray, T.L.; Irusta, S.; Brennan, P.M.; Lloyd-Jones, G.C.; Sieger, D.; Santamaría, J.; Unciti-Broceta, A. Gold-triggered uncaging chemistry in living systems. Angew. Chem. Int. Ed. Engl., 2017, 56(41), 12548-12552. [http://dx.doi.org/10.1002/anie.201705609]. [PMID: 28699691].
[14]
Miller, M.A.; Askevold, B.; Mikula, H.; Kohler, R.H.; Pirovich, D.; Weissleder, R. Nano-palladium is a cellular catalyst for in vivo chemistry. Nat. Commun., 2017, 8, 15906. [http://dx.doi.org/10.1038/ncomms15906]. [PMID: 28699627].
[15]
Li, B.; Liu, P.; Wu, H.; Xie, X.; Chen, Z.; Zeng, F.; Wu, S. A bioorthogonal nanosystem for imaging and in vivo tumor inhibition. Biomaterials, 2017, 138, 57-68. [http://dx.doi.org/10.1016/j.biomaterials.2017.05.036]. [PMID: 28554008].
[16]
Khan, I.; Seebald, L.M.; Robertson, N.M.; Yigit, M.V.; Royzen, M. Controlled in-cell activation of RNA therapeutics using bond-cleaving bio-orthogonal chemistry. Chem. Sci. (Camb.), 2017, 8(8), 5705-5712. [http://dx.doi.org/10.1039/C7SC01380A]. [PMID: 28989610].
[17]
Khan, I.; Agris, P.F.; Yigit, M.V.; Royzen, M. In situ activation of a doxorubicin prodrug using imaging-capable nanoparticles. Chem. Commun. (Camb.), 2016, 52(36), 6174-6177. [http://dx.doi.org/10.1039/C6CC01024E]. [PMID: 27076271].
[18]
Mejia Oneto, J.M.; Khan, I.; Seebald, L.; Royzen, M. In Vivo Bioorthogonal chemistry enables local hydrogel and systemic pro-drug to treat soft tissue sarcoma. ACS Cent. Sci., 2016, 2(7), 476-482. [http://dx.doi.org/10.1021/acscentsci.6b00150]. [PMID: 27504494].
[19]
Czuban, M.; Srinivasan, S.; Yee, N.A.; Agustin, E.; Koliszak, A.; Miller, E.; Khan, I.; Quinones, I.; Noory, H.; Motola, C.; Volkmer, R.; Di Luca, M.; Trampuz, A.; Royzen, M.; Mejia Oneto, J.M. Bio-orthogonal chemistry and reloadable biomaterial enable local activation of antibiotic prodrugs and enhance treatments against Staphylococcus aureus infections. ACS Cent. Sci., 2018, 4(12), 1624-1632. [http://dx.doi.org/10.1021/acscentsci.8b00344]. [PMID: 30648146].
[20]
Ji, X.; Pan, Z.; Yu, B.; De La Cruz, L.K.; Zheng, Y.; Ke, B.; Wang, B. Click and release: Bioorthogonal approaches to “on-demand” activation of prodrugs. Chem. Soc. Rev., 2019, 48(4), 1077-1094. [http://dx.doi.org/10.1039/C8CS00395E]. [PMID: 30724944].
[21]
Zheng, Y.; Ji, X.; Yu, B.; Ji, K.; Gallo, D.; Csizmadia, E.; Zhu, M.; Choudhury, M.R.; De La Cruz, L.K.C.; Chittavong, V.; Pan, Z.; Yuan, Z.; Otterbein, L.E.; Wang, B. Enrichment-triggered prodrug activation demonstrated through mitochondria-targeted delivery of doxorubicin and carbon monoxide. Nat. Chem., 2018, 10(7), 787-794. [http://dx.doi.org/10.1038/s41557-018-0055-2]. [PMID: 29760413].
[22]
Wang, P.; Zhou, J. Proteolysis targeting chimera (PROTAC): A paradigm-shifting approach in small molecule drug discovery. Curr. Top. Med. Chem., 2018, 18(16), 1354-1356. [http://dx.doi.org/10.2174/1568026618666181010101922]. [PMID: 30306871].
[23]
Lebraud, H.; Wright, D.J.; Johnson, C.N.; Heightman, T.D. Protein degradation by in-cell self-assembly of proteolysis targeting chimeras. ACS Cent. Sci., 2016, 2(12), 927-934. [http://dx.doi.org/10.1021/acscentsci.6b00280]. [PMID: 28058282].
[24]
Fan, X.; Ge, Y.; Lin, F.; Yang, Y.; Zhang, G.; Ngai, W.S.; Lin, Z.; Zheng, S.; Wang, J.; Zhao, J.; Li, J.; Chen, P.R. Optimized tetrazine derivatives for rapid bioorthogonal decaging in living cells. Angew. Chem. Int. Ed. Engl., 2016, 55(45), 14046-14050. [http://dx.doi.org/10.1002/anie.201608009]. [PMID: 27735133].
[25]
Carlson, J.C.T.; Mikula, H.; Weissleder, R. Unraveling tetrazine-triggered bioorthogonal elimination enables chemical tools for ultrafast release and universal cleavage. J. Am. Chem. Soc., 2018, 140(10), 3603-3612. [http://dx.doi.org/10.1021/jacs.7b11217]. [PMID: 29384666].

Rights & Permissions Print Cite
Article Metrics
89
24
2
2
© 2024 Bentham Science Publishers | Privacy Policy