Article
Chemistry, Multidisciplinary
Shaomin Lin, Zeyuan Mo, Peng Wang, Chunmao He
Summary: In order to meet the demand for peptide salicylaldehyde esters, we developed a new method for the preparation of these esters from peptide hydrazides through nitrite oxidation and phenolysis. This method is simple and suitable for both synthetic peptides and expressed proteins, facilitating peptide synthesis and the combined application of NCL and STL.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Hongxiang Wu, Yi Tan, Wai Lok Ngai, Xuechen Li
Summary: Chemical synthesis of hydrophobic proteins is challenging, but can be achieved by integrating peptide solubilizing strategies with peptide ligation. This study presents a tunable backbone modification strategy that allows for the introduction of a solubilizing tag for peptide purification and ligation processes. The effectiveness of this strategy was demonstrated by the chemical synthesis of interleukin-2.
Article
Chemistry, Multidisciplinary
Jiamei Liu, Tongyao Wei, Yi Tan, Heng Liu, Xuechen Li
Summary: This study introduces a new solubilizing tag strategy, utilizing reducible solubilizing tags (RSTs) introduced on the peptide chain for purifying and ligating peptides with poor solubility, featuring operational simplicity and readily accessible materials.
Article
Chemistry, Organic
Karnjit Parmar, Pouyan Haghshenas, Michel Gravel
Summary: This study presents the shortest synthesis of the glycosidase inhibitor (+)-hyacinthacine A(1) using a highly chemoselective N-heterocyclic carbene-catalyzed crossbenzoin reaction and a furan photooxygenation-amine cyclization strategy. The unprecedented cyclization on a furylic alcohol due to the instability of formed intermediates was successfully achieved, eventually leading to the formation of the requisite pyrrolizidine framework through a three-step one-pot process.
Article
Chemistry, Organic
Ya Wu, Ming Wang, Mei Xu, Sheng Liu
Summary: The Pictet-Spengler reaction of tryptamine and (5-methoxy-2-nitrophenyl)-glyoxal in hot AcOH can lead to a redox-mediated cyclization and reduction sequence, resulting in the formation of iheyamine A with a yield of 52%.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Jun-Jie Wang, Rui-Xue Bai, Mao-Qi Yang, Zheng-Yu Chen, Min-Dan Wang, Qian Zhao, Guo-Qiang Lin, Jian-Guo Fu, Chen-Guo Feng
Summary: The total synthesis of (-)-amathaspiramide A was achieved through the efficient construction of a chiral aza-spirobicyclic core using the aldol addition/transamidification cascade. The scope of the efficient construction methodology was investigated, and configuration adjustment via an asymmetric protonation process was identified as a vital step to obtain the correct stereochemistry.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Chemistry, Organic
Yan Zong, Xiaomei Zou, Jingyuan Song, Gen-Qiang Chen, Xumu Zhang
Summary: In this study, a highly efficient catalyst was developed to synthesize chlorohydrins and oxaheterocycles, and its advantages were demonstrated in the synthesis of key intermediates for drugs.
Article
Chemistry, Medicinal
Jinzheng Wang, Xuechen Li
Summary: Non-ribosomal cyclic peptides are abundant in natural sources and exhibit attractive bioactivities and favorable pharmacological properties. Their total synthesis can be achieved through peptide ligation, which offers advantages in cyclizing peptides. This strategy highlights the unique features of achieving total synthesis in cyclic peptide synthesis.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
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, Applied
Ana Milian, Lucia Sanchez-Jimenez, Jaime Tostado, Juan J. Vaquero, Manuel A. Fernandez-Rodriguez, Patricia Garcia-Garcia
Summary: The total synthesis of Laetevirenol A, a natural product with antioxidant activity, has been achieved using a gold-catalyzed cycloisomerization reaction. The construction of the phenanthrene moiety in Laetevirenol A was realized through this key step, which was influenced by the nature of substituents. Laetevirenol A was obtained in 10 steps from commercially available substrates, with a 20% global yield.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Multidisciplinary
Tomoya Mashiko, Yuta Shingai, Jun Sakai, Shogo Kamo, Shinya Adachi, Akinobu Matsuzawa, Kazuyuki Sugita
Summary: In this study, the first total synthesis of cochlearol B, a meroterpenoid natural product with a unique pentacyclic structure, was described. Key steps including oxidative cyclization and subsequent intramolecular [2+2] photocycloaddition allowed efficient access to cochlearol B with a longest linear sequence of 16 steps and 9% overall yield. Single-crystal X-ray crystallographic analysis confirmed the stereochemistry of cochlearol B.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Mizushi Yanagihara, Kanae Nakahara, Naoki Kishimoto, Towa Abe, Satoshi Miura, Shogo Misumi, Makoto Sako, Mitsuhiro Arisawa, Kenichi Murai
Summary: The first total synthesis of marine sesterterpenoid ansellone G (2) has been accomplished. The hydrobenzopyran skeleton of ansellone G (2) was synthesized through the Prins cyclization reaction of a chloro-substituted homoallyl alcohol. The HIV latency-reversing activity of the synthesized compounds was also evaluated.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Mizushi Yanagihara, Kanae Nakahara, Naoki Kishimoto, Towa Abe, Satoshi Miura, Shogo Misumi, Makoto Sako, Mitsuhiro Arisawa, Kenichi Murai
Summary: The first total synthesis of marine sesterterpenoid ansellone G and phorbadione was achieved, and their HIV latency-reversing activity was evaluated.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Sudip Shit, Bipin Kumar Behera, Subhamoy Biswas, Anil K. K. Saikia
Summary: A metal-free Lewis acid-initiated protocol has been developed for the synthesis of highly substituted 3-(dihydrofuran-3(2H)-ylidene)isobenzofuran-1(3H)-imines. The reaction involves the formation of dihydrofuranylidene carbocation followed by intramolecular cyclization, leading to the desired products in moderate to good yields. The methodology can also be extended to the synthesis of 3-(dihydro-2H-pyran-3(4H)-ylidene)-isobenzofuran-1(3H)-imines, and furanylidene isobenzofuranones can be obtained in excellent yields through post synthetic applications.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Jia-Xuan Liu, Shi-Peng Zhang, Feng-Sen Sun, Hui Li, Ya-Ling Gong, Shi-Chao Lu, Shu Xu
Summary: In this study, Naphthospironone A, a polyhydroxy cagelike bioactive natural product, was synthesized for the first time. The spiro[bicyclo[3.2.1]octane-pyran] core was constructed by an acid-promoted epoxide-opening lactonisation and a base-induced intramolecular aldol-type cyclisation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Pharmacology & Pharmacy
Esben B. Svenningsen, Jacob Thyrsted, Julia Blay-Cadanet, Han Liu, Shaoquan Lin, Jaime Moyano-Villameriel, David Olagnier, Manja Idorn, Soren R. Paludan, Christian K. Holm, Thomas B. Poulsen
Summary: The findings suggest that certain polyether ionophore antibiotics have potential as broad-spectrum antiviral agents, demonstrating an ability to inhibit the replication of SARS-CoV-2 in cells.
ANTIVIRAL RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Shaoquan Lin, Han Liu, Esben B. Svenningsen, Malene Wollesen, Kristian M. Jacobsen, Frederikke D. Andersen, Jaime Moyano-Villameriel, Christine N. Pedersen, Peter Norby, Thomas Torring, Thomas B. Poulsen
Summary: By recycling substructures from highly abundant natural polyether ionophores, analogues with enhanced selectivity towards bacterial cells have been successfully prepared, suggesting potential opportunities for future methodological innovation in the structural optimization of polyether ionophores.
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
Biochemistry & Molecular Biology
Lea Dichmann, Mikkel Bregnhoj, Han Liu, Michael Westberg, Thomas B. Poulsen, Michael Etzerodt, Peter R. Ogilby
Summary: Genetically encodable proteins that photosensitize the production of singlet oxygen will play an important role in elucidating cellular processes modulated by reactive oxygen species (ROS). However, caution should be exercised when using these tools to probe mechanisms of ROS-mediated processes.
PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES
(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
Zhenquan Sun, Wenjie Ma, Yihui Cao, Tongyao Wei, Xiaoyong Mo, Hoi Yee Chow, Yi Tan, Carina H. P. Cheung, Jiamei Liu, Hung Kay Lee, Edmund C. M. Tse, Han Liu, Xuechen Li
Summary: In this study, a superfast desulfurization strategy based on tetraethylborate was developed for the modification of complex biomacromolecules. This strategy is simple to operate and does not require special conditions. The authors also developed a one-pot native chemical ligation-desulfurization method for the synthesis of specific proteins.
Article
Chemistry, Physical
Tongyao Wei, Dongfang Li, Yue Zhang, Yubo Tang, Haiyan Zhou, Han Liu, Xuechen Li
Summary: Ortho-phthalaldehyde has been found to have wide potentials for protein bioconjugation and peptide cyclization. This study reports a second-generation dialdehyde-based peptide cyclization method using thiophene-2,3-dialdehyde (TDA) that reacts specifically with primary amine and thiol within unprotected peptides, generating a highly stable cyclic structure.
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
Chemistry, Multidisciplinary
Carina Hey Pui Cheung, Tin Hang Chong, Tongyao Wei, Han Liu, Xuechen Li
Summary: Recently, ortho-phthalaldehyde (OPA) has been used for the modification of proteins and peptides through OPA-amine two-component reactions and intramolecular OPA-amine-thiol three-component reactions. Guanidine has been discovered to be an effective additive in switching the intermolecular OPA-amine-thiol three-component reaction to a stoichiometric process, enabling the construction of peptide-peptide and peptide-drug conjugate structures. This reaction shows great versatility and flexibility, as demonstrated by the successful synthesis of model peptide-peptide and peptide-drug conjugates using unprotected peptides.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Wenjie Ma, Hongxiang Wu, Sha Liu, Tongyao Wei, Xiang David Li, Han Liu, Xuechen Li
Summary: This study developed a new strategy for the synthesis of peptide C-terminal salicylaldehyde esters using Boc-SPPS. The strategy utilized semicarbazone-modified aminomethyl resin and was compatible with all canonical amino acids.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Immunology
Peng Gao, Yuanxin Wei, Suying Hou, Pok-Man Lai, Han Liu, Sherlock Shing Chiu Tai, Victor Yat Man Tang, Pradeep Halebeedu Prakash, Kong-Hung Sze, Jonathan Hon Kwan Chen, Hongzhe Sun, Xuechen Li, Richard Yi-Tsun Kao
Summary: This study identified the first inhibitor of SaeR, a protein involved in regulating virulence factors in Staphylococcus aureus. The inhibitor, named HR3744, showed in vitro and in vivo effectiveness against S. aureus infections. The findings suggest that SaeR could be a potential target for the development of antivirulence drugs.
EMERGING MICROBES & INFECTIONS
(2023)
Review
Chemistry, Organic
Xing Guo, Pengfei Li, Han Liu, Xuechen Li
Summary: Bacteria resistant to antibiotics pose a threat to public health. Non-2-ulosonic acids, including pseudaminic acid, legionaminic acid, acinetaminic acid, fusaminic acid, and their epimers, are found in pathogenic Gram-negative bacteria and are believed to be associated with bacterial infection/pathogenicity and immune escape. Their unique structures and poorly understood biological functions make them attractive targets for synthetic studies and drug discovery. This review summarizes the chemical syntheses of four types of non-2-ulosonic acid structures reported in the past two decades and discusses recent progress in the application of synthetic non-2-ulosonic acid derivatives.
ORGANIC CHEMISTRY FRONTIERS
(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)
