Article
Chemistry, Multidisciplinary
Ziran Jiang, Aochiu Chen, Jeffrey Chen, Arman Sekhon, Gordon V. Louie, Joseph P. Noel, James J. La Clair, Michael D. Burkart
Summary: This study developed a probe based on the natural product cerulenin for fluorescent labeling and crosslinking to evaluate protein-protein interactions. Additionally, two new masked crosslinking probes were described for activity and structure studies of biosynthetic pathways.
Review
Clinical Neurology
Tobias Ruck, Falk Nimmerjahn, Heinz Wiendl, Jan D. Luenemann
Summary: Ruck et al. provide an overview of advancements in next-generation antibody-based therapies for brain diseases, focusing on Fc engineering and improving bioavailability in the CNS parenchyma. They discuss the potential benefits and limitations of these therapies in neurology. Antibody-based treatments have become standard in neuroinflammatory diseases, and efforts are being made to expand their use to a wider range of neurological disorders. The specificity and effectiveness of these treatments are determined by engineering the antigen-binding fragment (Fab) and the crystallizable fragment (Fc) of the antibodies. The development of technologies to enhance the bioavailability of these treatments within the brain shows promise for improving options for patients with limited therapeutic choices.
Article
Biochemical Research Methods
Roberta Lucchi, Maria C. Lucana, Montserrat Escobar-Rosales, Cristina Diaz-Perlas, Benjami Oller-Salvia
Summary: Antibody therapeutics have potential to treat various diseases, but side effects limit their safe dosage. Conditionally-active antibodies provide additional selectivity for improved safety. In this study, a versatile approach to conditionally mask antibody derivatives was proposed and successfully applied to cancer stem cells in multiple tumors. This method enables rapid activation of antibodies with different internal or external stimuli.
Article
Immunology
Ran Salomon, Rony Dahan
Summary: The clinical use of anti-CD40 agonist monoclonal antibodies faces challenges due to dose-limiting toxicity. Novel approaches are being explored to overcome the systemic toxicity associated with CD40 agonism.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Tian-Sheng Chen, Hao Long, Yuxing Gao, Hai-Chao Xu
Summary: The paper presents a practical and cost-efficient method using continuous flow reactors for the highly selective monooxygenation of benzylic C(sp(3))-H bonds. The method does not require catalysts or chemical oxidants, and the produced alcohols undergo facile hydrolysis. It exhibits a broad scope and exceptional site selectivity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Tian-Sheng Chen, Hao Long, Yuxing Gao, Hai-Chao Xu
Summary: This study presents a practical and cost-efficient electrochemical method for the highly selective monooxygenation of benzylic C(sp(3))-H bonds using continuous flow reactors. The method produces trifluoroacetate esters that are resistant to further oxidation but can be easily hydrolyzed to form benzylic alcohols during aqueous workup. It exhibits broad scope, exceptional site selectivity, and requires no catalysts or chemical oxidants.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Alan Burke, Florence Borot, Xing Du, Michael Churchill, Jian Ding, Albert Mridul Grass, Philip DeSouza, Abdullah Mahmood Ali, Siddhartha Mukherjee
Summary: This study presents a new method using synthetic orthogonal heterodimers to create a bispecific structure, and demonstrates its effectiveness in leukemia and T-cell mediated cytotoxicity. Additionally, it shows the efficacy of this method in extending survival and reducing leukemia in a mouse model. These results highlight the importance and clinical potential of this approach for bispecific antibodies.
Article
Chemistry, Multidisciplinary
Hongfei Chen, Hong-Chai Fabio Wong, Jiaming Qiu, Biquan Li, Dingdong Yuan, Hao Kong, Yishu Bao, Yu Zhang, Zhiyi Xu, Ying-Lung Steve Tse, Jiang Xia
Summary: Targeted immunotherapies use the binding capabilities of antibodies to enhance immune responses for long-term tumor destruction. A chemoenzymatic reaction has been developed to specifically modify a single tyrosine residue in therapeutic antibodies, allowing the attachment of fluorescent molecules or bioorthogonal groups. This reaction can be used to construct monofunctionalized antibody-drug conjugates and antibody/nanobody-conjugated effector cells, improving targeted cancer immunotherapy outcomes.
Article
Biochemistry & Molecular Biology
Hye Lim Choi, Ha Rim Yang, Ha Gyeong Shin, Kyusang Hwang, Ji Woong Kim, Ji Hyun Lee, Taehoon Ryu, Yushin Jung, Sukmook Lee
Summary: Antibody phage display is a crucial technology for discovering and developing target-specific monoclonal antibodies. This study constructed a large human combinatorial single-chain variable fragment library with high diversity, which can be used for the rapid development of recombinant human monoclonal antibodies for therapeutic and diagnostic applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Chemistry, Inorganic & Nuclear
Amrita Das, Supriya Rej, Tarun K. Panda
Summary: Organoboranes obtained from hydroboration reactions are important compounds that can provide valuable synthons for various transformations. Transition metals and main group metals have been used as catalysts, and aluminum complexes have recently gained attention as suitable candidates due to their abundance and low toxicity. The development of aluminum complexes for more efficient and stable catalytic systems is highly appreciated.
DALTON TRANSACTIONS
(2022)
Review
Pharmacology & Pharmacy
Manasa Gangadhar Shetty, Padmini Pai, Renita Esther Deaver, Kapaettu Satyamoorthy, Kampa Sundara Babitha
Summary: Acetylation and deacetylation of histone and non-histone proteins are important epigenetic processes involved in cancer regulation. Abnormal expression of histone deacetylases (HDACs) is common in various cancers, but pan-HDAC inhibition may not be effective due to isoform-specific overexpression in certain cancers. Therefore, isoform-selective HDAC inhibition could be a promising therapeutic strategy against cancer.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Tanner C. Jankins, Raul Martin-Montero, Phillippa Cooper, Ruben Martin, Keary M. Engle
Summary: This tungsten-catalyzed hydroboration of unactivated alkenes at distal C(sp(3))-H bonds with the aid of native directing groups is characterized by simplicity, exquisite regio- and chemoselectivity, and wide substrate scope, providing a complementary site-selectivity pattern to other metal-catalyzed borylation reactions and chain-walking protocols.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Tian-Xiang Luan, Lehan Du, Jia-Rui Wang, Keyu Li, Quan Zhang, Pei-Zhou Li, Yanli Zhao
Summary: This study presents a new covalent organic framework (COF) named PyPor-COF, which is a highly efficient photosensitizer. The COF combines photoactive porphyrin moieties through in situ-formed imidazole groups and exhibits high crystallinity, permanent porosity, robust stability, and semiconductive photo response activity. It can effectively initiate the generation of singlet oxygen (1O2) under visible-light irradiation, surpassing the efficiency of other porphyrin-based reactants and commercially available photosensitizing agents. The COF also shows potential in triggering 1O2 production in a physiological environment, making it a promising candidate for photodynamic therapy.
Review
Chemistry, Multidisciplinary
Huijae Park, Jung Jae Park, Phuong-Danh Bui, Hyeokjun Yoon, Costas P. Grigoropoulos, Daeho Lee, Seung Hwan Ko
Summary: The connection between laser-based material processing and additive manufacturing is deeply rooted. Laser can selectively solidify materials for additive manufacturing, allowing for customizability. Laser-based material processing is extensively studied and applied in manufacturing functional components with unique shapes or complex patterns.
ADVANCED MATERIALS
(2023)
Article
Chemistry, Multidisciplinary
Dan Liu, Kai Yang, Di Fang, Shi-Jun Li, Yu Lan, Yiyun Chen
Summary: This study reports the first method for generating formyl radicals from alpha-chloro N-methoxyphthalimides, which selectively synthesize aldehydes under mild photoredox conditions. The method exhibits excellent chemoselectivity and regioselectivity for installing aldehydes on various organic compounds.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemical Research Methods
Anders Dinesen, Alexander Winther, Archie Wall, Anders Maercher, Johan Palmfeldt, Vijay Chudasama, Jesper Wengel, Kurt Gothelf, James R. Baker, Kenneth A. Howard
Summary: This study aims to improve the stability of albumin-nucleic acid biomolecular drug designs by employing a fast hydrolyzing linker and nuclease resistant nucleotide analogues. The results show that the stabilized biomolecular constructs have high serum stability and retain module functionality, promoting the drug delivery potential of this biomolecular platform.
BIOCONJUGATE CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Richard J. Spears, Cliona McMahon, Monika Shamsabadi, Calise Bahou, Ioanna A. Thanasi, Lea N. C. Rochet, Nafsika Forte, Fabien Thoreau, James R. Baker, Vijay Chudasama
Summary: A thiol-labile cysteine protecting group based on an unsaturated pyridazinedione (PD) scaffold was reported, showing compatibility in solid phase peptide synthesis (SPPS) and applicability in microwave-assisted SPPS and native chemical ligation (NCL) in a model system.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Roshni Malde, Michael A. Parkes, Michael Staniforth, Jack M. Woolley, Vasilios G. Stavros, Vijay Chudasama, Helen H. Fielding, James R. Baker
Summary: Thiomaleimides undergo efficient intermolecular [2 + 2] photocycloaddition reactions but are limited to exo head-to-head isomers. A new intramolecular variation has been proposed, generating endo adducts with increased efficiency and reduced structural disturbance. The reaction applied to a protein scaffold increases thiol stability, and excited states studied through transient absorption spectroscopy provide insights into the reaction mechanism.
Review
Biochemistry & Molecular Biology
Fabien Thoreau, Vijay Chudasama
Summary: Immunotherapy has become one of the leading strategies for cancer treatment in the past two decades, with a growing number of related clinical trials. Despite significant progress, toxicity and resistance are still observed in some cases. The future direction may lie in multispecific antibody formats such as MuTICEMs and the application of bioconjugation chemistry.
RSC CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Organic
Roshni Malde, Daniel A. Richards, Luigia Salerno, Yanbo Zhao, Kersti Karu, Vijay Chudasama, James R. Baker
Summary: In this study, we describe the photodecarboxylations of substituted maleimides and the resulting elimination reactions, and demonstrate the ability to modulate the wavelength tunability through modification of double bond substituents. These versatile reagents, readily constructed and diversified by nucleophilic substitution reactions on bromomaleimides, are expected to provide new opportunities for triggered photorelease.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Fabien Thoreau, Peter A. Szijj, Michelle K. Greene, Lea N. C. Rochet, Ioanna A. Thanasi, Jaine K. Blayney, Antoine Maruani, James R. Baker, Christopher J. Scott, Vijay Chudasama
Summary: In recent years, there has been growing interest in protein-protein conjugation, especially in the context of bispecific antibodies (bsAbs) and their therapeutic applications. These molecules contain two paratopes capable of binding two distinct epitopes, enabling complex biological functions that monospecific antibodies cannot achieve. While traditional methods for bsAb construction involve protein engineering, recent developments have led to the emergence of chemical methods that offer increased modularity, speed, and the potential for further functionalization. However, most of these approaches lack the inclusion of a fragment crystallizable (Fc) modality, which provides effector function and increased half-life. In this study, a novel method using disulfide rebridging and click-chemistry has been reported for the generation of Fc-containing, IgG-like mono- and bispecific antibodies, referred to as synthetic antibodies (SynAbs). A T cell engager SynAb, FcCD20-(FabHER2)-FabCD3, has been successfully constructed and demonstrated the expected biological functions, including the ability to effectively kill HER2+ target cells in co-culture assays with T cells.
ACS CENTRAL SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Yanbo Zhao, Vijay Chudasama, James R. Baker
Summary: We synthesized and applied trifunctional reagents to modify the native, solvent accessible disulfide bonds in trastuzumab using dual-modality approach. The reagents were developed from the dibromomaleimide (DBM) platform with two orthogonal clickable functional groups built around a lysine core. We also developed an aryl diselenide additive that enables rapid reduction of antibody disulfide bonds in 4 minutes and a rapid overall reduction-bridging-double click sequence.
Review
Biochemistry & Molecular Biology
Richard J. Spears, Vijay Chudasama
Summary: Advances in site-specific chemical modification of proteins, specifically targeting cysteine residues or protein termini, have revolutionized the design of protein-based therapeutics. This review discusses recent strategies in this field and provides insights into future directions.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Peter A. Szijj, Melissa A. Gray, Mikaela K. Ribi, Calise Bahou, Joao C. F. Nogueira, Carolyn R. Bertozzi, Vijay Chudasama
Summary: Bispecific T cell engagers (BiTEs) can bring cancer cells close to cytotoxic T cells and promote their death. Checkpoint inhibitory T cell engagers (CiTEs) improve efficacy by reversing cancer-cell immune-dampening strategies. The chemical method described here allows for the generation of multi-protein constructs with further biological applications.
Article
Chemistry, Multidisciplinary
Fabien Thoreau, Lea N. C. Rochet, James R. R. Baker, Vijay Chudasama
Summary: In this article, a pyridazinedione-based trifunctional dual bridging linker was reported, which enables the generation of mAb-, Fab'-, or Fc-conjugates from native mAb, (Fab')(2), or Fc formats, respectively. The method allows for the production of various payload-antibody ratios (PARs), including heterofunctional PARs. The non-recombinant approach offers homogeneity, novelty, and accessibility to PARs, making it a suitable tool for optimizing antibody-drug conjugates and developing new antibody therapeutics.
Article
Chemistry, Multidisciplinary
Alina Chrzastek, Ioanna A. Thanasi, James A. Irving, Vijay Chudasama, James R. Baker
Summary: Disulfide bridging is a powerful strategy for constructing selective protein bioconjugates. This study introduces a new class of reagents with a stable-labile design, allowing for robust attachment to one cysteine residue and reactive handle for subsequent bioconjugation at the other. By incorporating thioesters, the reagents can undergo native chemical ligation with N-terminal cysteines, expanding the scope of disulfide bridging strategies.
Article
Chemistry, Multidisciplinary
Nehaal Ahmed, Richard J. Spears, Tom D. Sheppard, Vijay Chudasama
Summary: In this study, the authors reported a method for the formation of new C-C bonds through the activation of C-H bonds using oxygen. The process involves the generation of radical intermediates in an oxygen atmosphere, which can then undergo functionalization on saturated heterocycles and ethers. The method provides access to a range of acetylenic and vinyl substituted saturated heterocycles with synthetic significance.
Article
Chemistry, Multidisciplinary
Richard J. Spears, Alina Chrzastek, Steven Y. Yap, Kersti Karu, Abil E. Aliev, James R. Baker, Vijay Chudasama
Summary: In this study, we report a significant discovery regarding the use of tris(dialkylamino)phosphine reagents in peptide and protein modification. We found that C-terminal thiophosphonium species can be selectively and rapidly generated from their disulfide counterparts, with unique stability. In contrast, internal thiophosphonium species degrade quickly. We demonstrated this chemoselectivity on a model peptide and an antibody fragment, and characterized the species in various small molecule/peptide studies.
CHEMICAL COMMUNICATIONS
(2022)
Review
Chemistry, Organic
Calise Bahou, Vijay Chudasama
Summary: Tools for chemical modification of peptides and proteins are attracting increasing interest in chemical biology due to their versatile applications. Cysteine residues and disulfide bonds are ideal targets for modification, and pyridazinediones (PDs) play a crucial role in site-selective modification.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Review
Chemistry, Multidisciplinary
Richard J. Spears, Cliona McMahon, Vijay Chudasama
Summary: The use of protecting groups for the cysteine thiol group has allowed for advancements in peptide and protein chemistry, enabling the synthesis of complex disulfide-rich peptides, protein semisynthesis, and labeling both in vitro and in vivo. Researchers have developed over 60 individual protecting groups for cysteine, showcasing their importance in peptide synthesis and protein science.
CHEMICAL SOCIETY REVIEWS
(2021)
Review
Chemistry, Multidisciplinary
Dan He, Yawen Li, Fuwen Zhao, Yuze Lin
Summary: High trap density in organic solar cells leads to localized charge carriers and reduced carrier lifetime, limiting device efficiency. This feature article summarizes the recent advances of trap suppression by material design and device engineering.
CHEMICAL COMMUNICATIONS
(2024)
Review
Chemistry, Multidisciplinary
Olivier Monfort, Arshitha Madhusudhan, Martin Motola
Summary: This article presents the advantages of coupling photocatalysis and Fenton-based processes for environmental remediation and discusses their synergy. It critically examines the simultaneous triggering of these two processes and provides insights into research approaches. The study aims to enhance understanding of this complex process and highlight the potential integration of new catalysts in current wastewater treatment technology.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Manideepa Dhar, Chittaranjan Mishra, Avijit Das, Uttam Manna
Summary: An approach of 'polymerization of monomers in its aggregated form' has been introduced to tailor the water wettability of fibrous and porous substrates, achieving hydrophobicity to superhydrophobicity transition, as well as patterned wettability. This facile chemical method provides a durable coating with adjustable and patterned wettability for various potential applications.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Saswat Ranjan Bhoi, Chhanda Debnath, Shikha Gandhi
Summary: In this article, a novel catalytic reaction using Pd(0) and Bronsted acid is reported for the synthesis of biologically important imidazolidinone-fused N-heterocycles through redox-neutral intramolecular N-allylation of indoles and pyrroles with alkynes. This atom-economical method is applicable to a wide range of substrates and eliminates the need for leaving groups or oxidizing agents commonly used in traditional allylation reactions.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Longkun Chen, Mingshuai Zhang, Meichen Liu, Zhuoyuan Liu, Yuetong Qiu, Zhilai Zhang, Fuchao Yu, Jiuzhong Huang
Summary: In this study, an efficient Rh(III)-catalyzed selective mono- and dual-C-H bond functionalization/cyclization with iodonium ylide as the sole coupling partner was demonstrated. Fused benzodiazepine skeletons were obtained in excellent yields, providing an improved approach to dual C-H unsymmetrical functionalization.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Alice Kennett, Sven Epple, Gabriella van der Valk, Irene Georgiou, Evelyne Gout, Romain R. Vives, Angela J. Russell
Summary: This study presents the design and synthesis of sulfated disaccharide inhibitors based on IdoA(2S)-GlcNS(6S), which showed potent inhibition of Sulf-2. The results suggest that IdoA(2S)-GlcNS(6S) is the shortest fragment size required for effective inhibition of Sulfs, and a trisulfated disaccharide is identified as the minimal fragment size of heparan sulfate for effective endosulfatase inhibition.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Mauro Garbini, Andrea Brunetti, Riccardo Pedrazzani, Magda Monari, Massimo Marcaccio, Giulio Bertuzzi, Marco Bandini
Summary: The self-adaptability of galvanostatic electrolysis was found to be helpful in a multistage chemo- and diastereoselective electrochemically promoted cyclodimerization of chalcones. Through a series of reductive events, densely functionalized cyclopentanes with five contiguous stereocenters were obtained (25 examples, yields up to 95%, dr values up to >20:1). Further experimental and electrochemical investigations indicated the crucial role of dynamic kinetic resolution of the aldol intermediate in the reaction mechanism.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Dhananjay S. Nipate, Neha Meena, Prakash N. Swami, Krishnan Rangan, Anil Kumar
Summary: In this study, the synthesis of functionalized benzo[a]phenazines and indazolo[2,3-a]quinolines was achieved through Rh(III)-catalyzed oxidative annulation of 2-arylquinoxalines and 2-aryl-2H-indazoles with allyl alcohols. The method showed a wide substrate scope, excellent functional group tolerance, good to high yields of annulated products, and the capability for scaled-up synthesis. A tentative mechanism of the annulation reaction was proposed based on a preliminary mechanistic investigation.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Ruonan Zhang, Abudukadi Tudi, Xia Yang, Xuping Wang, Zhihua Yang, Shujuan Han, Shilie Pan
Summary: A new lead tellurium borate material with a unique fundamental building block [B4O10] was synthesized and found to exhibit high birefringence. The structure-property relationship was discussed using first-principles calculations.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Amresh Kumar Singh, Baishali Thakurta, Anupam Giri, Monalisa Pal
Summary: This study introduces three key concepts for the quick synthesis of large-scale high-quality 2D materials films and their utilization in device fabrication.
CHEMICAL COMMUNICATIONS
(2024)
Article
Chemistry, Multidisciplinary
Reina Hagiwara, Shun Nishimura, Kosuke Okeyoshi
Summary: A copolymer-conjugated nanocatalytic system has been developed to improve electron transfer and enhance photoinduced H2 generation.
CHEMICAL COMMUNICATIONS
(2024)
