Article
Chemistry, Multidisciplinary
Lujuan Xu, Maria J. S. A. Silva, Pedro M. P. Gois, Seah Ling Kuan, Tanja Weil
Summary: The development of bioconjugation chemistry has created new classes of protein conjugates with functions beyond what Nature can provide, but there is still a lack of reagents that can tune reactivity to different amino acid residues. By modifying 2-chloromethyl acryl reagents, selective protein modification at cysteine or disulfide sites can be achieved.
Article
Chemistry, Multidisciplinary
Angus S. Mackay, Richard J. Payne, Lara R. Malins
Summary: Electrochemical strategies for peptide and protein modification offer promising prospects for building molecular complexity, overcoming limitations of existing bioconjugation strategies, and achieving chemoselective bioconjugation chemistry.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Anuchit Phanumartwiwath, Chatchai Kesornpun, Daranee Chokchaichamnankit, Amnart Khongmanee, Penchatr Diskul-Na-Ayudthaya, Theetat Ruangjaroon, Chantragan Srisomsap, Prasat Kittakoop, Jisnuson Svasti, Somsak Ruchirawat
Summary: This article describes a new catalyst-free approach to modify proteins through 1,3-dipolar cycloaddition. The protein containing dehydroalanine (Dha) reacts with nitrile oxides generated in situ, resulting in the formation of a new isoxazoline ring at a pre-defined site. The installation of 1-pyrene isoxazoline on annexin V allows it to act as a fluorescent probe for labeling apoptosis in human cholangiocarcinoma cells (HuCCA-1).
Article
Chemistry, Multidisciplinary
Jiyue Chen, Roberto J. Brea, Alessandro Fracassi, Christy J. Cho, Adrian M. Wong, Marta Salvador-Castell, Sunil K. Sinha, Itay Budin, Neal K. Devaraj
Summary: A new method has been developed to synthesize lipids through chemical reactions under physiological conditions, producing cell-like micron-sized vesicles similar to natural phospholipid membranes.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Rhys C. Griffiths, Frances R. Smith, Diyuan Li, Jasmine Wyatt, David M. Rogers, Jed E. Long, Lola M. L. Cusin, Patrick J. Tighe, Robert Layfield, Jonathan D. Hirst, Manuel M. Mueller, Nicholas J. Mitchell
Summary: This article introduces a visible-light-mediated reaction that enables site-selective modification of peptides and proteins via desulfurative C(sp(3))-C(sp(3)) bond formation. The reaction is rapid and high yielding in peptide systems, with comparable translation to proteins. Using this chemistry, a range of moieties is installed into model systems and an effective PTM-mimic is successfully integrated into a recombinantly expressed histone.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
E. Dalles Keyes, Marcus C. Mifflin, Maxwell J. Austin, Brighton J. Alvey, Lotfa H. Lovely, Andriea Smith, Tristin E. Rose, Bethany A. Buck-Koehntop, Jyoti Motwani, Andrew G. Roberts
Summary: Inspired by oxidation-induced modifications in nature, a selective strategy for the preparation of Tyr-linked cyclic peptides has been developed. This approach utilizes N4-substituted 1,2,4-triazoline-3,5-diones (TADs) as azo electrophiles to react chemoselectively with the phenolic side chain of Tyr residues, forming stable C-N1-linked cyclic peptides.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Hwaseok Hong, Uk-Jae Lee, Seul Hoo Lee, Hyun Kim, Gyu-Min Lim, Sang-Hyuk Lee, Hyeoncheol Francis Son, Byung-Gee Kim, Kyung-Jin Kim
Summary: This study reports a tyrosinase called SaTYR from Streptomyces avermitilis that has higher activity against tyrosine residues on the protein surface compared to other tyrosinases. The crystal structure of SaTYR was determined, revealing a relatively flat and shallow substrate-binding pocket. The study also provides a structural rationale for determining the optimal positions for introducing target tyrosine residues in SaTYR-mediated protein modification.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2024)
Article
Chemistry, Multidisciplinary
Kuei-Chien Tang, Jian Cao, Lisa M. Boatner, Linwei Li, Jonathan Farhi, Kendall N. Houk, Jennifer Spangle, Keriann M. Backus, Monika Raj
Summary: Researchers developed a new series of tunable amine-reactive electrophiles (TAREs) to address the poor hydrolytic stability of activated esters as covalent inhibitors. These TAREs form stable adducts with lysine and generate another reactive electrophiles for lysine on reaction with cysteine, showing higher hydrolytic stability and potential as covalent ligands.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Christian E. Stieger, Yerin Park, Mark A. R. de Geus, Dongju Kim, Christiane Huhn, J. Sophia Slenczka, Philipp Ochtrop, Judith M. Muechler, Roderich D. Suessmuth, Johannes Broichhagen, Mu-Hyun Baik, Christian P. R. Hackenberger
Summary: We have discovered ethynyl-triazolyl-phosphinates (ETPs) as a new class of electrophilic warheads with cysteine selectivity for bioconjugation. Through Cu-I-catalyzed azide alkyne cycloaddition (CuAAC), various functional electrophilic building blocks, including proteins, were obtained from diethynyl-phosphinate. ETP-reagents were used to create fluorescent peptide-conjugates for receptor labeling on live cells and stable and biologically active antibody-drug conjugates. The excellent cysteine selectivity of ETP-electrophiles was demonstrated in mass spectrometry-based, proteome-wide cysteine profiling, highlighting their potential for homogeneous bioconjugation strategies to connect complex biomolecules.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Ksenia Ksenofontova, Anastasia A. Kerner, Alexander A. Ksenofontov, Artyom Yu Shagurin, Pavel S. Bocharov, Michael M. Lukanov, Airat R. Kayumov, Darya E. Zhuravleva, Zalina I. Iskhakova, Evgeniy E. Molchanov, Dmitriy A. Merkushev, Ilya A. Khodov, Yuriy S. Marfin
Summary: A reactive boron-dipyrromethene (BODIPY) derivative was synthesized for labeling proteins with amino groups. Its spectroscopic properties and sensitivity in protein detection were investigated. The results showed that this fluorescent dye has high sensitivity for protein detection.
Article
Chemistry, Multidisciplinary
Wang Wan, Yanan Huang, Qiuxuan Xia, Yulong Bai, Yuwen Chen, Wenhan Jin, Mengdie Wang, Di Shen, Haochen Lyu, Yuqi Tang, Xuepeng Dong, Zhenming Gao, Qun Zhao, Lihua Zhang, Yu Liu
Summary: The study reveals that covalent Michael addition can occur during protein aggregation, offering a new pathway for chemical reactions. By designing covalent probes for imaging, chemical proteomics, and therapeutic purposes, different fluorescence color-switch responses can be achieved.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Nino Trattnig, Zeshi Li, Gerlof P. Bosman, Paul Kosma, Geert-Jan Boons
Summary: This article describes a method for the controlled multi-functionalization of the carrier protein CRM197, allowing for the conjugation of a carbohydrate-based antigen and an immune potentiator. The approach involves selective reduction and disulfide rebridging, ensuring efficient protein modification and covalent attachment of the immune potentiator. Site-specific conjugation avoids alteration of the carrier protein's epitopes and allows for efficient immune potentiation.
Article
Chemistry, Multidisciplinary
Rhys C. Griffiths, Frances R. Smith, Jed E. Long, Daniel Scott, Huw E. L. Williams, Neil J. Oldham, Robert Layfield, Nicholas J. Mitchell
Summary: The article presents a technique for site-selective installation of modified sidechains into peptides and proteins using visible-light-mediated reaction, which is simple, rapid, and shows potential for various applications.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Rhys C. Griffiths, Frances R. Smith, Jed E. Long, Daniel Scott, Huw E. L. Williams, Neil J. Oldham, Robert Layfield, Nicholas J. Mitchell
Summary: This technology enables rapid, operationally simple, and tolerant to ambient atmosphere installation of a range of lysine (Lys) PTMs into model peptide systems. It also demonstrates the potential of this technology by site-selectively installing an NeAc sidechain into recombinantly expressed ubiquitin (Ub).
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Ramesh Adakkattil, Kalyani Thakur, Vishal Rai
Summary: The article outlines the research progress in the past decade regarding the precise engineering of native proteins through chemical methods. Developments include chemoselective and site-selective labeling, modular modification, protein-specificity, and site-specificity technologies. Additionally, biotechnology tools such as Maspecter (R) have been introduced to accelerate detailed analysis of bioconjugates and enhance the toolbox for homogeneous antibody-drug conjugates (ADCs).
Article
Toxicology
Qiwen Liao, Shengnan Li, Shirley Weng In Siu, Jean-Etienne R. L. Morlighem, Clarence Tsun Ting Wong, Xiufen Wang, Gandhi Radis-Baptista, Simon Ming-Yuen Lee
ARCHIVES OF TOXICOLOGY
(2019)
Article
Toxicology
Qiwen Liao, Guiyi Gong, Terence C. W. Poon, Irene L. Ang, Kate M. K. Lei, Shirley Weng In Siu, Clarence Tsun Ting Wong, Gandhi Radis-Baptista, Simon Ming-Yuen Lee
ARCHIVES OF TOXICOLOGY
(2019)
Article
Chemistry, Medicinal
Summer Y. Y. Ha, Roy C. H. Wong, Clarence T. T. Wong, Dennis K. P. Ng
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Chemistry, Multidisciplinary
Yue Zhang, Qing Zhang, Clarence T. T. Wong, Xuechen Li
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2019)
Article
Chemistry, Organic
Clarence T. T. Wong, Jacky C. H. Chu, Summer Y. Y. Ha, Roy C. H. Wong, Gaole Dai, Tsz-Tung kwong, Chi-Hang Wong, Dennis K. P. Ng
Article
Chemistry, Medicinal
Jacky C. H. Chu, Wing-Ping Fong, Clarence T. T. Wong, Dennis K. P. Ng
Summary: A facile procedure was developed for in situ peptide cyclization and phthalocyanine conjugation, resulting in three cyclic peptide-phthalocyanine conjugates with advanced photosensitizer properties, one of which showed selective uptake by EGFR-positive cancer cell lines and effective inhibition of tumor growth in vivo.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Xiufen Wang, Qiwen Liao, Hanbin Chen, Guiyi Gong, Shirley Weng In Siu, Qian Chen, Hiotong Kam, Carolina Oi Lam Ung, Kwok-Kuen Cheung, Gandhi Radis-Baptista, Clarence Tsun Ting Wong, Simon Ming-Yuen Lee
Summary: PcActx peptide, a potential TRPV1 channel blocker, exhibits prominent anti-epileptic activity possibly through modulating calcium signaling and GABAergic-glutamatergic signaling.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Toxicology
Hanbin Chen, Shirley Weng In Siu, Clarence Tsun Ting Wong, Jianwen Qiu, Alex Kwok-Kuen Cheung, Simon Ming Yuen Lee
Summary: This study analyzed the transcriptome of the branching coral Acropora digitifera and discovered three polypeptides, named AdKuz1, AdKuz2, and AdKuz3, that showed a close relationship to Kunitz-type peptides. AdKuz1 and AdKuz2 exhibited anti-inflammatory effects and suppressed the epileptic effects induced by pentylenetetrazol (PTZ) in zebrafish. AdKuz2 particularly showed superior anti-epileptic effects and affected the synthesis of glutamate and GABA, as well as enhancing the activity of the GABA(A) receptor.
ARCHIVES OF TOXICOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Junlong Xiong, Jacky C. H. Chu, Wing-Ping Fong, Clarence T. T. Wong, Dennis K. P. Ng
Summary: This study presents a novel bioconjugation strategy for the selective delivery of modified enzymes into cancer cells, enabling the activation of photosensitizers for therapeutic applications. The activation of photosensitizers inside the cancer cells resulted in cell death, demonstrating the potential of this approach for efficient photodynamic therapy.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Jacky C. H. Chu, Clarence T. T. Wong, Dennis K. P. Ng
Summary: In this study, a novel dual receptor-mediated bioorthogonal activation approach was developed to enhance the tumor specificity of photodynamic therapy. By targeted delivery and specific activation of photosensitizers, the photodynamic action was confined to cancer cells that overexpress both the biotin receptor and epidermal growth factor receptor (EGFR).
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Materials Science, Biomaterials
Jacky C. H. Chu, Chihao Shao, Summer Y. Y. Ha, Wing-Ping Fong, Clarence T. T. Wong, Dennis K. P. Ng
Summary: This study presents a one-pot approach to cyclise a tumour-targeting peptide and conjugate it on red blood cells loaded with a boron dipyrromethene-based photosensitiser. The surface modification with cyclic RGD peptide moieties enhances photocytotoxicity by selectively binding against alpha(v)beta(3) integrin-overexpressed cancer cells. This facile strategy proves to be effective for live-cell surface modification across various applications.
BIOMATERIALS SCIENCE
(2021)
Article
Pharmacology & Pharmacy
Jacky C. H. Chu, Miu Ling Chin, Clarence T. T. Wong, Mamie Hui, Pui-Chi Lo, Dennis K. P. Ng
Summary: This study presents a facile synthetic approach to prepare a phthalocyanine-based photosensitizer conjugated with a cyclic bactenecin peptide, which shows selective affinity toward bacteria and synergistic cytotoxic effects against a spectrum of multidrug-resistant bacterial strains. The inhibition mechanism is believed to be based on the physical destruction of the cell membrane due to the cyclic peptide followed by photodynamic action induced by the phthalocyanine unit.
ADVANCED THERAPEUTICS
(2021)
Article
Chemistry, Multidisciplinary
Jacky C. H. Chu, Caixia Yang, Wing-Ping Fong, Clarence T. T. Wong, Dennis K. P. Ng
CHEMICAL COMMUNICATIONS
(2020)
Article
Chemistry, Multidisciplinary
Evelyn Y. Xue, Roy C. H. Wong, Clarence T. T. Wong, Wing-Ping Fong, Dennis K. P. Ng
Proceedings Paper
Infectious Diseases
Kwang Poo Chang, Bala K. Kolli, Chia-Kwung Fan, Dennis K. P. Ng, Clarence T. T. Wong, Laura Manna, Raffaele Corso, Neng-Yao Shih, Robert Elliott, X. P. Jiang, Shin-Hong Shiao, Guo-Liang Fu
LIGHT-BASED DIAGNOSIS AND TREATMENT OF INFECTIOUS DISEASES
(2018)