Article
Chemistry, Multidisciplinary
Tanausu Santos, David S. Rivero, Yaiza Perez-Perez, Endika Martin-Encinas, Jorge Pasan, Antonio Hernandez Daranas, Romen Carrillo
Summary: A dynamic nucleophilic aromatic substitution of tetrazines (S(N)Tz) is introduced, allowing for the easy obtainment of compound libraries or complex molecular structures with post-functionalization capabilities through inverse electron demand Diels-Alder (IEDDA) reaction. The obtained structures can be disassembled under UV irradiation or suitable chemical reagents. This methodology has been demonstrated to be highly promising in building responsive supramolecular systems.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Lukas Hoff, Simon D. Schnell, Andrea Tomio, Anthony Linden, Karl Gademann
Summary: A silver-mediated Pd-catalyzed cross-coupling method for 3-bromo-1,2,4,5-tetrazine with boronic acids was presented in this study. It was found that electronic modification of the dppf ligand played a crucial role in achieving good turnover. Using this fast method, a variety of alkyl-, heteroatom-, and halide-substituted aryl- and heteroaryl-tetrazines were successfully prepared, with yields up to 87%.
Article
Chemistry, Multidisciplinary
Nicole Houszka, Hannes Mikula, Dennis Svatunek
Summary: 1,2,4,5-Tetrazines are widely used in bioorthogonal chemistry for their high reactivity in Diels-Alder reactions. The substituents in the 3- and 6-positions of the tetrazine scaffold significantly affect the rate of cycloadditions, but this is not explained by frontier molecular orbital interactions. Instead, the high reactivity of mono-substituted tetrazines is due to decreased Pauli repulsion, leading to a more asynchronous approach and reduced distortion energy. Additionally, ethylene is not a good model compound for other alkenes in Diels-Alder reactions.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Organic
Ilya Nechaev, Georgij Cherkaev, Nikolay Boev, Pavel N. Solyev
Summary: A new three-component reaction has been discovered, which can synthesize compounds with specific structure under mild conditions and high functional group tolerance, selectively functionalizing pyridines, and the reaction mechanism involves a rare [4+2] cycloaddition step.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Review
Chemistry, Multidisciplinary
Lisa Maria Haiber, Markus Kufleitner, Valentin Wittmann
Summary: The IEDDA reaction is a bioorthogonal ligation reaction that is emerging as a versatile tool in metabolic glycoengineering. It allows for the introduction of unnatural sugar derivatives with chemical reporter groups into cellular glycans, enabling visualization or isolation of glycoconjugates.
FRONTIERS IN CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Zhi-Chen Wu, K. N. Houk, Dale L. Boger, Dennis Svatunek
Summary: This study investigates the reaction mechanism of 1,2,3-triazines and 1,2,3,5-tetrazine with amidines, revealing that the reaction proceeds through an addition/N-2 elimination/cyclization pathway. Contrary to previous expectations, the rate-limiting step in this transformation is the initial nucleophilic attack of amidines on azine C4.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Vincente T. Sterrenberg, Doerte Stalling, J. Iven H. Knaack, Timothy K. Soh, Jens B. Bosse, Chris Meier
Summary: The metabolic labeling of nucleic acids in living cells is a valuable method to track nucleic acid metabolism dynamics and gain insights into cellular biology and pathogen-host interactions. However, the narrow substrate window of endogenous kinases limits the use of highly reactive moieties for intracellular labeling of DNA. In this study, a TriPPPro approach was utilized to deliver a 2TCOa-modified 2'-deoxycytidine triphosphate into living cells, allowing metabolic incorporation into cellular and viral DNA, which can be visualized using a two-step labeling strategy.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Zixi Zhu, Dale L. Boger
Summary: This article describes the second example of selective N1/N4 1,4-cycloaddition of 1,2,4,5-tetrazines with preformed or in situ generated enamines, promoted by the Lewis acid ZnCl2, with an expanded scope. The reaction involves a formal [4 + 2] cycloaddition across two nitrogen atoms (N1/N4 vs C3/C6) of a 1,2,4,5-tetrazine, followed by retro [4 + 2] cycloaddition, loss of a nitrile, and aromatization to provide 1,2,4-triazines. The optimization of reaction parameters, the simplification of the reaction through in situ enamine generation from ketones, the definition of the enamine reaction scope, and the exploration of the tetrazine scope are detailed, along with representative applications of the product 1,2,4-triazines. The work establishes and extends a powerful method for the efficient one-step regioselective synthesis of 1,2,4-triazines directly from easily accessible ketones, overcoming challenges in conventional approaches.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Eva Bokor, Dora T. Kecskes, Ferenc Gombas, Alexandra Feher, Eszter Kardos, Akram Dabian, Zsofia Vonza, Eszter Szennyes, Laszlo Somsak
Summary: This paper investigates the synthesis of C-glycopyranosyl tetrazines and their application in various reactions.
NEW JOURNAL OF CHEMISTRY
(2022)
Article
Chemistry, Physical
Anamarija Bris, Yasujiro Murata, Yoshifumi Hashikawa, Davor Margetic
Summary: Novel 2-pyridyl-sym-tetrazines bearing a guanidine functional group were synthesized and their reactivity was studied. Experimental and computational results showed that guanidine sym-tetrazines exhibit high reactivity towards strained polycyclic alkenes, while reactions with C-60 fullerene were less successful. These findings provide important insights into the cycloaddition reactivity and potential synthetic utility of tetrazine derivatives.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Chemistry, Multidisciplinary
Chika Yamamoto, Minori Suzuki, Suguru Yoshida
Summary: A facile method for synthesizing pyridazines from 1,2,4,5-tetrazines and alkynes is described. The reaction is significantly accelerated by 1,1,1,3,3,3-hexafluoro-2-propanol. The wide applicability and predictable regioselectivity of this method make it useful for the synthesis of various substituted pyridazines.
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN
(2022)
Article
Chemistry, Organic
Li-Wen Shen, Zhen-Hua Wang, Yong You, Jian-Qiang Zhao, Ming-Qiang Zhou, Wei-Cheng Yuan
Summary: An unprecedented (3+1) cyclization of alpha-nitro-sostyrenes, generated in situ from alpha-bromooximes, and N-tosyloxycarbamates was developed, enabling the synthesis of a range of structurally unique and hitherto unexplored 2,3-dihydrodiazete N-oxides in moderate to high yields. The products possess a highly strained four-membered ring structure containing two nitrogen atoms. The synthetic applicability of the products was also demonstrated by many important conversions to diverse nitrogen-containing compounds.
Article
Chemistry, Organic
Mahshid Hamzehloueian, Mina Haghdadi
Summary: The mechanisms of domino reactions between TTZs and alkynes were studied using DFT method. The reactions proceed through an aza Diels-Alder (ADA) step and a retro Diels-Alder (rDA) step leading to the formation of aromatic rings. The ADA step of TTZ 1 and ynamine 3 reaction follows a stepwise mechanism, while TTZ 2 and ynamine 3 reaction proceeds through a stepwise mechanism. The ADA reactions of cyclooctyne 4 with TTZs 1 and 2 occur through a two-stage one-step mechanism and a symmetric synchronous one-step mechanism, respectively.
Article
Chemistry, Multidisciplinary
Takuya Miyazaki, Shaoyi Chen, Stelios Florinas, Kazunori Igarashi, Yu Matsumoto, Tatsuya Yamasoba, Ze-Qi Xu, Herren Wu, Changshou Gao, Kazunori Kataoka, R. James Christie, Horacio Cabral
Summary: This study presents a Hoechst-based reporter system that can monitor the release and engagement of drugs from nanoparticle delivery systems. The system allows the visualization of drug distribution and binding to subcellular targets, providing insights into the effects of drug-linker and nanoparticle properties on target-bound drug distribution. The findings from this study were applied to develop highly potent, targeted anticancer nanoparticles with optimized drug-linker design, resulting in effective tumor growth inhibition without severe toxicity.
Article
Chemistry, Physical
Bartosz Jedrzejewski, Mateusz Musiejuk, Justyna Doroszuk, Dariusz Witt
Summary: The study has developed simple and efficient methods for the synthesis of unsymmetrical vinyl disulfides with additional functional groups under mild conditions. These methods involve reactions between S-vinyl phosphorodithioate and thiotosylates, allowing for the synthesis of vinyl disulfides with various additional functionalities. Furthermore, the vinyl disulfides react with transient o-iminothioquinones in an inverse electron-demand [4+2] cycloaddition to yield benzo[b][1,4]thiazine derivatives.
Article
Radiology, Nuclear Medicine & Medical Imaging
Denis R. Beckford-Vera, Alba Gonzalez-Junca, Jessica S. Janneck, Tony L. Huynh, Joseph E. Blecha, Youngho Seo, Xiaojuan Li, Henry F. VanBrocklin, Benjamin L. Franc
MOLECULAR IMAGING AND BIOLOGY
(2020)
Article
Medicine, Research & Experimental
Sinan Wang, Charles Blaha, Raquel Santos, Tony Huynh, Thomas R. Hayes, Denis R. Beckford-Vera, Joseph E. Blecha, Andrew S. Hong, Miko Fogarty, Thomas A. Hope, David R. Raleigh, David M. Wilson, Michael J. Evans, Henry F. VanBrocklin, Tomoko Ozawa, Robert R. Flavell
MOLECULAR PHARMACEUTICS
(2019)
Article
Oncology
Denis R. Beckford Vera, Shaun D. Fontaine, Henry F. VanBrocklin, Brian R. Hearn, Ralph Reid, Gary W. Ashley, Daniel V. Santi
MOLECULAR CANCER THERAPEUTICS
(2020)
Article
Multidisciplinary Sciences
En-Chi Hsu, Meghan A. Rice, Abel Bermudez, Fernando Jose Garcia Marques, Merve Aslan, Shiqin Liu, Ali Ghoochani, Chiyuan Amy Zhang, Yun-Sheng Chen, Aimen Zlitni, Sahil Kumar, Rosalie Nolley, Frezghi Habte, Michelle Shen, Kashyap Koul, Donna M. Peehl, Amina Zoubeidi, Sanjiv S. Gambhir, Christian A. Kunder, Sharon J. Pitteri, James D. Brooks, Tanya Stoyanova
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Multidisciplinary Sciences
Aimen Zlitni, Gayatri Gowrishankar, Idan Steinberg, Tom Haywood, Sanjiv Sam Gambhir
NATURE COMMUNICATIONS
(2020)
Article
Oncology
Alba Gonzalez-Junca, Oliver Reiners, Luis D. Borrero-Garcia, Denis Beckford-Vera, Ann A. Lazar, William Chou, Steve Braunstein, Henry VanBrocklin, Benjamin L. Franc, Mary Helen Barcellos-Hoff
Summary: The study investigates the potential of using PET imaging to detect TGF beta activation in tumors, showing that radiation therapy induces TGF beta activation, and TGF beta blockade provides survival benefit only in the context of radiation treatment.
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2021)
Article
Oncology
Shaun D. Fontaine, Gary W. Ashley, Peter J. Houghton, Raushan T. Kurmasheva, Morgan Diolaiti, Alan Ashworth, Cody J. Peer, Ryan Nguyen, William D. Figg, Denis R. Beckford-Vera, Daniel Santi
Summary: A long-acting prodrug of the PARP inhibitor talazoparib was prepared and characterized in this study, showing that a single injection of the prodrug in murine xenografts provided tumor suppression equivalent to a month of daily dosing of talazoparib. This long-lasting antitumor effect was attributed to the prodrug's long t(1/2), high exposure of released TLZ, increased tumor sensitivity upon continued exposure, and tumor accumulation.
Article
Oncology
Sinan Wang, Jun Li, Jun Hua, Yang Su, Denis R. Beckford-Vera, Walter Zhao, Mayuri Jayaraman, Tony L. Huynh, Ning Zhao, Yung-hua Wang, Yangjie Huang, Fujun Qin, Sui Shen, Daniel Gioeli, Robert Dreicer, Renuka Sriram, Emily A. Egusa, Jonathan Chou, Felix Y. Feng, Rahul Aggarwal, Michael J. Evans, Youngho Seo, Bin Liu, Robert R. Flavell, Jiang He
Summary: The novel CD46-targeted PET radiopharmaceutical [Zr-89]DFO-YS5 shows specific binding and uptake in human prostate cancer models, including PSMA-negative and AR-negative tumors, demonstrating potential for clinical translation as an imaging agent and biomarker in prostate cancer.
CLINICAL CANCER RESEARCH
(2021)
Article
Nanoscience & Nanotechnology
Yun-Sheng Chen, Yang Zhao, Corinne Beinat, Aimen Zlitni, En-Chi Hsu, Dong-Hua Chen, Friso Achterberg, Hanwei Wang, Tanya Stoyanova, Jennifer Dionne, Sanjiv Sam Gambhir
Summary: In this study, targetable nanodroplets containing hypertonic saline solution were developed for molecular imaging of prostate cancer in animal models. This targeted approach showed increased specificity compared to untargeted nanodroplets or prostate cancer cells that did not express the specific receptor. The use of ultra-high-frequency radio-frequency acoustic molecular imaging with biocompatible targeted contrast agents presents a safe diagnostic option, with potential for improved in vivo applications.
NATURE NANOTECHNOLOGY
(2021)
Review
Oncology
J. Sven D. Mieog, Friso B. Achterberg, Aimen Zlitni, Merlijn Hutteman, Jacobus Burggraaf, Rutger-Jan Swijnenburg, Sylvain Gioux, Alexander L. Vahrmeijer
Summary: Fluorescence-guided surgery (FGS) using tumor-targeted imaging agents has emerged as a promising method for intraoperative cancer detection in the past decade, but its clinical implementation is still in the early stages. The key to success lies in the coordination of target selection, imaging agents, and detection systems to achieve real-time intraoperative visualization for the benefit of cancer patients.
NATURE REVIEWS CLINICAL ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Louise Kiru, Aimen Zlitni, Aidan Michael Tousley, Guillermo Nicolas Dalton, Wei Wu, Famyrah Lafortune, Anna Liu, Kristen May Cunanan, Hossein Nejadnik, Todd Sulchek, Michael Eugene Moseley, Robbie G. Majzner, Heike Elisabeth Daldrup-Link
Summary: The study introduces a new approach to label CAR T cells with iron oxide nanoparticles, enabling noninvasive detection of the CAR T cells in solid tumors. The results show that labeled CAR T cells could locate to osteosarcomas and off-target sites, while unlabeled cells were not visible. This study provides a new method for monitoring the location of CAR T cells in solid tumors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Denis R. Beckford-Vera, Robert R. Flavell, Youngho Seo, Enrique Martinez-Ortiz, Maya Aslam, Cassandra Thanh, Emily Fehrman, Marion Pardons, Shreya Kumar, Amelia N. Deitchman, Vahid Ravanfar, Brailee Schulte, I-Wei Katherine Wu, Tony Pan, Jacqueline D. Reeves, Christopher C. Nixon, Nikita S. Iyer, Leonel Torres, Sadie E. Munter, Tony Hyunh, Christos J. Petropoulos, Rebecca Hoh, Benjamin L. Franc, Lucio Gama, Richard A. Koup, John R. Mascola, Nicolas Chomont, Steven G. Deeks, Henry F. VanBrocklin, Timothy J. Henrich
Summary: In this study, the authors utilized positron emission tomography (PET) imaging to visualize the tissue-wide burden of HIV in infected individuals using a radiolabeled broadly neutralizing antibody, Zr-89-VRC01. They found that PET tracer uptake in lymph nodes positively correlates with HIV protein levels measured directly from cells obtained from these tissues. This strategy could provide a non-invasive way to characterize residual HIV infection in the context of therapeutic interventions.
NATURE COMMUNICATIONS
(2022)
Article
Computer Science, Interdisciplinary Applications
Idan Steinberg, Jeesu Kim, Martin K. Schneider, Dongwoon Hyun, Aimen Zlitni, Sarah M. Hopper, Tal Klap, Geoffrey A. Sonn, Jeremy J. Dahl, Chulhong Kim, Sanjiv Sam Gambhir
Summary: The SPANNER algorithm is a new robust algorithm for photoacoustic imaging that can reconstruct images in real-time and address artifacts associated with limited viewing angles and imaging depth. Comparisons with other reconstruction algorithms and experiments on tissue samples and prostate cancer patients demonstrate SPANNER's ability to improve contrast to background ratio and axial resolution, as well as accurately quantify PA signals from contrast agents.
IEEE TRANSACTIONS ON MEDICAL IMAGING
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Timothy J. Henrich, Terry Jones, Denis Beckford-Vera, Patricia M. Price, Henry F. VanBrocklin
Article
Oncology
Friso B. Achterberg, Babs G. Sibinga Mulder, Ruben P. J. Meijer, Bert A. Bonsing, Henk H. Hartgrink, J. Sven D. Mieog, Aimen Zlitni, Seung-min Park, Arantza Farina Sarasqueta, Alexander L. Vahrmeijer, Rutger-Jan Swijnenburg
ANNALS OF TRANSLATIONAL MEDICINE
(2020)