Article
Chemistry, Multidisciplinary
Xuan Liang, Shan Qian, Zhizheng Lou, Renming Hu, Yuchen Hou, Peng R. Chen, Xinyuan Fan
Summary: The development of a biocompatible photocatalytic technology termed CAT-NIR enables the spatiotemporal manipulation of biological processes in living animals using external near infrared light (NIR). This system utilizes Os(II) terpyridine complex as an efficient NIR photocatalyst for deboronative hydroxylation reactions, resulting in the release of bioactive molecules. CAT-NIR also allows for the regulation of affibody binding to cell surface receptors through genetic code expansion and computer-aided screening, providing a selective cell tagging technology with external NIR light.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Patrick Keppel, Barbara Sohr, Walter Kuba, Marion Goldeck, Philipp Skrinjar, Jonathan C. T. Carlson, Hannes Mikula
Summary: Bond-cleavage reactions triggered by bioorthogonal tetrazine ligation have been used to chemically control the function of (bio)molecules and activate prodrugs. However, current methods for releasing phenols are limited. To address this issue, we developed a self-immolative linker that connects cleavable amines and phenols, allowing for controlled release of prodrugs.
Article
Chemistry, Physical
Valerio Sabatino, V. B. Unnikrishnan, Goncalo J. L. Bernardes
Summary: Bioorthogonal chemistry provides powerful tools for studying and manipulating biological systems without interfering with biological processes. The possibility of using bioorthogonal tools for prodrug activation is a promising area of research, which is currently progressing towards clinical trials. Metal-mediated bioorthogonal cleavage reactions have limitations in biological media, but they have been engineered for applications such as the release of small molecules.
Review
Chemistry, Multidisciplinary
Rui Huang, Cristina-Maria Hirschbiegel, Victor Lehot, Liang Liu, Yagiz Anil Cicek, Vincent M. Rotello
Summary: This review provides an overview of recent advances in the field of bioorthogonal nanozymes, focusing on the modular design of nanomaterials and catalysts and their synergistic engineering for in situ uncaging of imaging and therapeutic agents. Bioorthogonal nanozymes enable in situ drug synthesis at disease sites through prodrug activation. The role of nanomaterials in stabilizing and regulating transition metal catalysts is investigated, emphasizing their modular design.
ADVANCED MATERIALS
(2023)
Article
Chemistry, Multidisciplinary
Mengyang Chang, Feng Gao, Devin Pontigon, Giri Gnawali, Hang Xu, Wei Wang
Summary: A bioorthogonal on-demand prodrug strategy was developed to selectively activate and release PROTACs in cancer cells. The strategy utilizes a Tetrazine-modified RGD peptide as an activation component for targeted degradation of proteins of interest (POIs) in cancer cells. The results demonstrate selective activation of the PROTACs in an integrin alpha(v)beta(3)-dependent manner for protein degradation in cancer cells.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Review
Chemistry, Multidisciplinary
Stefano Fedeli, Jungkyun Im, Sanjana Gopalakrishnan, James L. Elia, Aarohi Gupta, Dongkap Kim, Vincent M. Rotello
Summary: Bioorthogonal transformations are chemical reactions that use pathways inaccessible to biological processes, providing new approaches for imaging and therapeutic strategies. Transition metal catalysts are widely employed as bioorthogonal catalysts, but face challenges in direct application in living systems, which can be addressed by incorporating them into nanomaterial scaffolds.
CHEMICAL SOCIETY REVIEWS
(2021)
Review
Chemistry, Multidisciplinary
Zhengwei Liu, Mengyu Sun, Wenting Zhang, Jinsong Ren, Xiaogang Qu
Summary: Bioorthogonal chemistry is a promising tool for studying biological processes in their natural environment. Recent research has focused on its potential in medical treatment, as it allows in situ drug synthesis for improved efficacy and reduced side effects. This minireview highlights the design and development of targeted bioorthogonal reactions for precise medical treatment, providing strategies for achieving target-specific reactions and emphasizing their application for different therapeutic targets.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Nanoscience & Nanotechnology
Stefano Fedeli, Rui Huang, Yavuz Oz, Xianzhi Zhang, Aarohi Gupta, Sanjana Gopalakrishnan, Jessa Marie V. Makabenta, Stephanie Lamkin, Amitav Sanyal, Yisheng Xu, Vincent M. Rotello
Summary: Bioorthogonal activation of pro-dyes and prodrugs using transition-metal catalysts provides a promising strategy for imaging and therapeutic applications. Stable and biodegradable nanocatalysts were created by loading transition-metal catalysts into polymeric nanoparticles. These nanocatalysts demonstrated therapeutic potential for effective treatment of bacterial biofilms through pro-antibiotic activation.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Chemistry, Multidisciplinary
Sixiao Liu, Zhenyuan Teng, Hang Liu, Tianyi Wang, Guoxiu Wang, Qiang Xu, Xiuyun Zhang, Min Jiang, Chengyin Wang, Wei Huang, Huan Pang
Summary: This study investigates a new type of graphene-embedded Ce-based UiO-66 photocatalyst (GSCe) with remarkable nitrogen fixation efficiency under solar light, making it a promising environmentally friendly solar fertilizer for crop cultivation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Chun Liu, Jingsheng Niu, Tingting Cui, Jinsong Ren, Xiaogang Qu
Summary: In this study, a near-infrared light-controllable carbonaceous nanocalabash motor catalyst was developed for active targeted synthesis of drugs inside biofilms. The catalyst exhibited good biocompatibility and rapid autonomous motion, enabling the generation of active molecules in deep biofilm layers to remove biofilms and eradicate bacteria.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Nanoscience & Nanotechnology
Jianjun Cheng, Xinyu Li, Shu Wang, Ying Han, Haitian Zhao, Xin Yang
Summary: This study demonstrated the excellent antitumor therapeutic effects of carrier-free photosensitive prodrugs BA-S-S/Ce6 NPs, showcasing their synergistic enhancement in cancer therapy. Molecular dynamics simulations and density functional theory calculations elucidated the assembly mechanism and improved singlet oxygen generation mechanism of the nanoparticles.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Article
Multidisciplinary Sciences
Yawen You, Qingqing Deng, Yibo Wang, Yanjuan Sang, Guangming Li, Fang Pu, Jinsong Ren, Xiaogang Qu
Summary: This study reports on a DNA-based biocompatible, highly efficient, and precisely targeted copper nanocatalyst, which exhibits excellent catalytic activity and achieves efficient prodrug activation and antitumor effects in cancer cells.
NATURE COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Melissa O. N. van de L'isle, Mari Carmen Ortega-Liebana, Asier Unciti-Broceta
Summary: The incorporation of abiotic transition metal catalysis into the field of chemical biology has expanded the bioorthogonal chemistry toolbox, with a variety of catalysts showing compatibility with physiological conditions and stability in complex environments. Current trends focus on exploring new metals and advanced catalytic devices, as well as integrating subcellular, cell- and site-targeting capabilities for novel biomedical applications. Transition metals play an increasing role in the controlled release of therapeutics, highlighting their potential in the field.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2021)
Article
Chemistry, Organic
Lani J. Davies, Laura M. Shuttleworth, Xiaobai Zhang, Sherry Peng, Christoph Nitsche
Summary: The biocompatible synthesis of constrained peptides is achieved by a straightforward method to introduce N-terminal ketones and aminooxy side chains during solid-phase peptide synthesis. Cyclization occurs spontaneously after acidic cleavage or in aqueous buffer. Protease inhibitors with varying conformational constraint are successfully synthesized, and the most constrained peptide exhibits an activity 2 orders of magnitude higher than its linear analog.
Article
Nanoscience & Nanotechnology
Dajiao Cheng, Rong Liu, Limei Tian, Quan Zhou, Fushuang Niu, Yinghong Yue, Ke Hu
Summary: The study presents a photocatalytic reaction that reduces nitrobenzene to aniline, which is significant for a class of nitroaromatic prodrugs in cancer therapy. The carefully designed photocatalyst achieves high selectivity in activating nitroaromatic prodrugs.
ACS APPLIED NANO MATERIALS
(2021)
Article
Biochemistry & Molecular Biology
Sarah J. Farley, Luca Salassa, Ana M. Pizarro, Peter J. Sadler
Summary: Platinum(II) complexes containing N,N-chelating ligand phenylazopyridine have been synthesized and characterized to investigate the effects of monodentate ligands and phenyl substituents on their absorption spectra and photoactivation. The complexes exhibit redshift and photoactivity, with strong contributions from chlorido and azido groups. Further analysis through spectroscopy and theoretical calculations elucidates the mechanism behind their photoactivation.
PHOTOCHEMISTRY AND PHOTOBIOLOGY
(2022)
Article
Public, Environmental & Occupational Health
Antonio Lopez-Gay, Jeroen Spijker, Helen V. S. Cole, Antonio G. Marques, Margarita Triguero-Mas, Isabelle Anguelovski, Marc Mari-Dell'Olmo, Juan A. Modenes, Dolores alamo-Junquera, Fernando Lopez-Gallego, Carme Borrell
Summary: This study investigated the relationship between COVID-19 incidence and sociodemographic factors in Barcelona. The findings showed that areas with higher population density, an aged population structure, a high presence of nursing homes, a higher proportion of people who left their residential areas during lockdown, and a higher proportion of people working in health-related occupations were more likely to have a higher number of COVID-19 cases. On the other hand, COVID-19 incidence was negatively associated with the percentage of residents with post-secondary education and the population born in countries with a high Human Development Index.
JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH
(2022)
Article
Chemistry, Physical
Guillermo Garcia-Marquina, Reyes Nunez-Franco, Francesca Peccati, Yi Tang, Gonzalo Jimenez-Oses, Fernando Lopez-Gallego
Summary: This study reveals that mutation clusters in the acyltransferase LovD9 can enhance enzyme kinetics and stability, providing a theoretical basis for simvastatin synthesis. By combining rational mutation clusters, we successfully generated the variant LovD-BuCh2 with catalytic efficiency close to LovD9.
Article
Chemistry, Physical
Stefano Scoditti, Eslam Dabbish, German E. Pieslinger, Elixabete Rezabal, Xabier Lopez, Emilia Sicilia, Luca Salassa
Summary: The mechanism for the photocatalytic activation of Pt(iv) anticancer prodrugs by riboflavin in the presence of NADH has been investigated. The results demonstrate that riboflavin accelerates the hydride transfer from NADH to riboflavin in the excited state, and facilitates the reduction of Pt(iv) complexes via an inner sphere mechanism.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2022)
Article
Chemistry, Multidisciplinary
Lorena Betancor, Fernando Lopez-Gallego
Summary: This review explores the combination of isolated enzymes and whole cells for chemical biomanufacturing. Both isolated enzymes and whole-cell biocatalysis have their own advantages, which can be synergistically utilized to improve efficiency and sustainability in bioprocesses. Different architectural approaches, such as combining extracellular enzymes and microorganisms, displaying enzymes on whole cell walls, and integrating enzymes and microorganisms into different materials, are presented as available alternatives for tandem enzyme-cell systems' biotransformations.
CURRENT OPINION IN GREEN AND SUSTAINABLE CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Susana Velasco-Lozano, Javier Santiago-Arcos, Maria Grazia Rubanu, Fernando Lopez-Gallego
Summary: In this study, a cell-free enzyme system with self-sufficient cofactor recycling was used for efficient transformation of aliphatic diols into omega-hydroxy acids. Two compatible alcohol dehydrogenases were selected as specialist biocatalysts to maximize the efficiency of the biosynthetic route. The cell-free system achieved high conversion rates and exhibited excellent enantioselectivity. It also demonstrated superior sustainability compared to traditional metal catalysts and whole cells. Moreover, the system allowed for enzyme reutilization.
Editorial Material
Chemistry, Multidisciplinary
Lorena Betancor, Fernando Lopez-Gallego
CURRENT OPINION IN GREEN AND SUSTAINABLE CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Guillermo Garcia-Marquina, Judith Langer, Mercedes Sanchez-Costa, Gonzalo Jimenez-Oses, Fernando Lopez-Gallego
Summary: This study focuses on optimizing the continuous synthesis of simvastatin by immobilizing an engineered acyltransferase enzyme on controlled porous glass particles functionalized with Fe3+-catechol complexes. The immobilized enzyme showed improved thermal stability and maintained high product yield during multiple operational cycles. Under optimal flow conditions, the system achieved a 100% simvastatin yield with improved reaction mass efficiency and atom economy compared to previous studies.
ACS SUSTAINABLE CHEMISTRY & ENGINEERING
(2022)
Article
Biochemistry & Molecular Biology
Giovanni Canil, Juan Gurruchaga-Pereda, Simona Braccini, Lorella Marchetti, Tiziana Funaioli, Fabio Marchetti, Alessandro Pratesi, Luca Salassa, Chiara Gabbiani
Summary: Photoactivatable Pt(IV) prodrugs have great potential as metal-based drugs due to their chemical inertness in oxidized form and selective targeting compared to Pt(II) compounds. A new Pt(IV) complex, soluble in water and unreactive until reduction, was synthesized. The complex exhibited rapid and efficient photoreduction with visible light, facilitated by a catalytic system based on flavin and NADH. The reactivity of the prodrug against biological targets was only observed after photoreduction to its Pt(II) analogue.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Physical
Oksana Azpitarte, Ane Zudaire, Jon Uranga, Xabier Lopez, Luca Salassa, Elena Formoso, Elixabete Rezabal
Summary: The unconventional bioorthogonal catalytic activation of anticancer metal complexes by flavin and flavoproteins photocatalysis has been recently reported. The reactivity is based on a two-electron redox reaction of the photoactivated flavin. In addition, site mutagenesis has been found to modulate and improve the catalytic activity of mini Singlet Oxygen Generator protein (SOG). The redox properties of flavin and the resulting reactivity of miniSOG are modulated by specific mutations, which is consistent with experimental results.
Article
Chemistry, Inorganic & Nuclear
Juan Sanchez-Camacho, Sonia Infante-Tadeo, Ana C. Carrasco, Stefano Scoditti, A'lvaro Martinez, Fabienne Barroso-Bujans, Emilia Sicilia, Ana M. Pizarro, Luca Salassa
Summary: In this study, two new asymmetric Pt(IV) derivatives were designed and synthesized, which could be effectively activated into toxic Pt(II) species by incubation with nicotinamide adenine dinucleotide, sodium ascorbate, and glutathione in the dark and under light irradiation. One of the derivatives displayed enhanced toxicity in MDA-MB-231 breast cancer cells preincubated with ascorbate, suggesting selective triggering of oxaliplatin generation through redox activation. Covalent binding of the flavin to the Pt complex was shown to be pivotal for this effect.
INORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Eleftheria Diamanti, Susana Velasco-Lozano, Daniel Grajales-Hernandez, Alejandro H. Orrego, Desire Di Silvio, Jose Maria Fraile, Fernando Lopez-Gallego
Summary: Self-sufficient heterogeneous biocatalysts (ssHB) are potential candidates for cofactor-dependent enzymes in chemical biomanufacturing. By immobilizing adenylated cofactors on agarose microbeads through reversible covalent bonds formed between the cis-diol of the ribose in the cofactor backbone and boronic acid, the limitations of current ssHBs in high ionic strength conditions are overcome. The functionality and stability of these ssHBs are demonstrated in reductive aminations, and the immobilized enzymes and cofactors can be reused multiple times.
ACS SUSTAINABLE CHEMISTRY & ENGINEERING
(2023)
Article
Chemistry, Multidisciplinary
Laura F. Mazzei, Juan Gurruchaga-Pereda, Alvaro Martinez, Javier Calvo Martinez, Luca Salassa, Aitziber L. Cortajarena
Summary: In this study, a multifunctional hybrid was developed for controlling the delivery and activation of Pt anticancer agents in vitro. Consensus tetratricopeptide repeat protein (CTPR) was used to covalently co-anchor riboflavin (photocatalyst) and a Pt(iv) prodrug complex. The Pt-loaded flavoprotein induced a 40% reduction in PANC-1 cell viability through the photocatalytic formation of cisplatin.
CHEMICAL COMMUNICATIONS
(2023)
Article
Materials Science, Multidisciplinary
Alessandro Silvestri, Faxing Wang, Xinliang Feng, Aitziber L. Cortajarena, Maurizio Prato
Summary: Enzymes, immobilized in a protein-based matrix, contribute to an enzymatic amperometric biosensor with exceptional stability and sensitivity. The use of electrochemically exfoliated graphene as an electroactive material enhances the sensor's performance in detecting lactate. The engineered protein film provides outstanding enzymatic stabilization, preserving the device sensitivity for over 6 months at room temperature.
JOURNAL OF MATERIALS CHEMISTRY C
(2022)
