Article
Chemistry, Organic
Xiao-Lei Xie, Jing-Ze Qi, Xiao-Cui Wan, Suo-De Zhang, Yan-Ni Zhang, Ge-Min Fang
Summary: We present a robust and practical method for chemical protein synthesis using an o-nitrobenzyl group as a temporary protective group. Through further investigation, we establish a reliable strategy for the quantitative photodeprotection of the o-nitrobenzyl group. This stable protective group is successfully applied in the chemical synthesis of a programmed death ligand 1 fragment, providing a practical approach for hydrazide-based native chemical ligation.
Article
Chemistry, Multidisciplinary
Mohadeseh Dastpeyman, John A. Karas, Azin Amin, Bradley J. Turner, Fazel Shabanpoor
Summary: Cell penetrating peptides (CPPs) are efficient vectors for intracellular delivery of biologically active agents like therapeutic antisense oligonucleotides (ASOs). Conjugating ASOs to CPPs through native chemical ligation (NCL) significantly improves their cellular permeability and therapeutic efficacy. This study demonstrates that chemo-selective NCL is a superior strategy for synthesizing bi-/trifunctional CPP-ASO conjugates with high efficiency.
FRONTIERS IN CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Luisa Maria Gatzemeier, Franc Meyer, Ulf Diederichsen, Tiago Fleming Outeiro
Summary: Alpha-Synuclein is a protein involved in neurodegenerative disorders that accumulate in brain protein inclusions. We have developed a chemical synthesis method for Alpha-Synuclein, allowing the synthesis of protein variants for further investigation of its structure and aggregation behavior.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Sebastian Trunschke, Emanuele Piemontese, Olaf Fuchs, Skander Abboud, Oliver Seitz
Summary: By introducing new ligation auxiliaries, this study expands the applicability of native chemical ligation and investigates the role of the pyridine-ring nitrogen in the auxiliaries. The study successfully synthesizes peptides with special structures, demonstrating that the new auxiliary has increased stability and wide application potential.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Ivan Sanchez-Campillo, Judit Miguel-Gracia, Periklis Karamanis, Juan B. Blanco-Canosa
Summary: Chemical protein synthesis is a consolidated field that utilizes the high chemospecificity of amide-forming reactions, particularly the native chemical ligation (NCL), alongside new technologies such as the Ser/Thr ligation and the alpha-ketoacid-hydroxylamine (KAHA) condensation. The NCL was initially designed for the ligation of peptides with a C-terminal thioester and an N-terminal cysteine. This study combines the Nbz and Bt approaches in a versatile linker, 1,2-diaminobenzene (Dbz), demonstrating high yields of ligation and the potential for transseleoesterification reactions. The results indicate faster NCL kinetics with Bt precursors, enabling rapid transthioesterification.
Article
Chemistry, Multidisciplinary
Richard Houska, Marvin Bjorn Stutz, Oliver Seitz
Summary: The study presents a reaction system for synthesizing Bcr-Abl tyrosine kinase inhibitors in water using native chemical ligation to form benzanilides. This method was successfully applied for the synthesis of thiolated ponatinib and GZD824 derivatives, with only a moderate effect on the affinity for Abl1 kinase. Nucleic acid-templated benzanilide formation could potentially find application in DNA-encoded combinatorial libraries for drug discovery.
Review
Chemistry, Multidisciplinary
Vangelis Agouridas, Nathalie Ollivier, Jerome Vicogne, Vincent Diemer, Oleg Melnyk
Summary: The last two decades have witnessed the rise in power of chemical protein synthesis, which now constitutes an established corpus of synthetic methods effectively complementing biological approaches. The emergence of chemoselective reactions enabling the formation of native peptide bonds between unprotected peptidic segments has contributed to this evolution. These native ligation reactions have fueled the production of homogeneous batches of large and highly decorated protein targets and have found successful applications in various fields such as chemical biology, medicinal chemistry, materials science, and nanotechnology research.
ACCOUNTS OF CHEMICAL RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Olaf Fuchs, Sebastian Trunschke, Hendrik Hanebrink, Marc Reimann, Oliver Seitz
Summary: This study introduces a new auxiliary, MPyE, designed to catalyze ligation reactions in chemical protein synthesis. The MPyE auxiliary proves to be effective in providing useful rates even for junctions containing proline or a beta-branched amino acid.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Dipankar Chaudhuri, Rajasekaran Ganesan, Alicia Vogelaar, Mansour A. Dughbaj, Paul M. Beringer, Julio A. Camarero
Summary: A new epimerization-free approach for the Fmoc-based synthesis of murepavadin using intramolecular native chemical ligation and desulfurization reaction has been developed, resulting in a high yield of bioactive murepavadin in two steps. The synthetic peptide antibiotic showed potent activity against different clinical isolates of P. aeruginosa. This approach can be easily adapted for the production of murepavadin analogues and other backbone-cyclized peptides.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Nathalie Ollivier, Eliott Roy, Vangelis Agouridas, Vincent Diemer, Oleg Melnyk
Summary: 4-Mercaptophenylacetic acid (MPAA) is a commonly used catalyst for native chemical ligation (NCL), but it requires a large excess for practical rates (up to 50-100 equivalents). In this study, we found that the catalytic potency of MPAA can be enhanced by introducing a stretch of arginines in the departing thiol of the thioester. This electrostatically assisted NCL reaction allows for rapid synthesis using substoichiometric concentrations of MPAA, which is advantageous for practical applications.
Article
Chemistry, Multidisciplinary
Skander A. Abboud, El Hadji Cisse, Michel Doudeau, Helene Benedetti, Vincent Aucagne
Summary: One of the main limitations in the chemical synthesis of proteins through NCL is the limited solubility of some peptide segments. A common solution is to derivatize the segment with a temporary solubilizing tag, which can be introduced on the thioester segment and removed concomitantly with the NCL reaction. This approach has been generalized to N-terminal cysteinyl segment counterparts and can be easily automated.
Review
Chemistry, Multidisciplinary
Sam M. Rowe, David R. Spring
Summary: RiPPs are recognized as a potential source of antimicrobial drugs due to their potent activity and high stability, but issues such as low solubility and poor bioavailability often hinder their clinical development. Chemical synthesis can help overcome some of these challenges, and the structural complexity of RiPPs makes them interesting synthetic targets.
CHEMICAL SOCIETY REVIEWS
(2021)
Article
Chemistry, Multidisciplinary
Wyatt C. Powell, Ruiheng Jing, Maciej A. Walczak
Summary: Deposits of the microtubule-associated protein Tau (MAPT) are characteristic of tauopathies, neurodegenerative diseases. This article describes the chemical synthesis of the longest isoform of Tau, 2N4R, and successfully prepares it using solid-phase peptide synthesis. The strategy involves the use of cysteine sites for ligations and modern protein chemistries to introduce post-translational modifications. This synthesis method can be applied to shorter isoforms of Tau and the introduction of modifications associated with tauopathies such as Alzheimer's disease.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Organic
Avijit K. Adak, Yung-Yu Su, Wei-Hao Wang, Chin-Lan Lin, Hao Gu, Yi-Chen Huang, Zhe-Jie Zhang, Chai-Lin Kao, Chun-Cheng Lin
Summary: Photoactivatable ligation auxiliaries simplify protein assembly by cleaving the auxiliary after ligation through photolysis. This study introduces an easy-to-attach TmNpE-auxiliary at the internal side-chain of N-terminal peptide fragments, enabling long-range ligation and photolytic removal in an aqueous buffer. The method's versatility is demonstrated by synthesizing a hPD-L1 peptide inhibitor. The TmNpE group offers easy introduction, compatibility with peptide ligation reactions, and mild cleavage conditions.
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.
Letter
Cell Biology
Qing-Yan Guo, Long-Hua Zhang, Chao Zuo, Dong-Liang Huang, Zhipeng A. Wang, Ji-Shen Zheng, Chang-Lin Tian
Review
Chemistry, Multidisciplinary
Yun-Kun Qi, Yan-Yan Si, Shan-Shan Du, Jun Liang, Ke-Wei Wang, Ji-Shen Zheng
SCIENCE CHINA-CHEMISTRY
(2019)
Article
Chemistry, Multidisciplinary
Baochang Zhang, Qiang Deng, Chong Zuo, Bingjia Yan, Chao Zuo, Xiu-Xiu Cao, Ting F. Zhu, Ji-Shen Zheng, Lei Liu
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2019)
Article
Chemistry, Multidisciplinary
Qian Qu, Shuai Gao, Fangming Wu, Meng-Ge Zhang, Ying Li, Long-Hua Zhang, Donald Bierer, Chang-Lin Tian, Ji-Shen Zheng, Lei Liu
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2020)
Article
Chemistry, Multidisciplinary
Dong-Liang Huang, Cedric Montigny, Yong Zheng, Veronica Beswick, Ying Li, Xiu-Xiu Cao, Thomas Barbot, Christine Jaxel, Jun Liang, Min Xue, Chang-Lin Tian, Nadege Jamin, Ji-Shen Zheng
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2020)
Article
Chemistry, Multidisciplinary
Dong-Liang Huang, Ying Li, Jun Liang, Lu Yu, Min Xue, Xiu-Xiu Cao, Bin Xiao, Chang-Lin Tian, Lei Liu, Ji-Shen Zheng
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2020)
Article
Multidisciplinary Sciences
Cedric Montigny, Dong Liang Huang, Veronica Beswick, Thomas Barbot, Christine Jaxel, Marc le Maire, Ji-Shen Zheng, Nadege Jamin
Summary: The study reveals the significant regulatory role of Sarcolipin on SERCA1a, affecting calcium and ATP binding and transport activity. Palmitoylation is not necessary for SLN's association with SERCA1a, but has a small but statistically significant effect on SERCA1a phosphorylation.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Ji-Shen Zheng, Jun Liang, Wei-Wei Shi, Ying Li, Hong-Gang Hu, Chang-Lin Tian, Lei Liu
Summary: This technology utilizes mirror-image proteins to encode and store information, which may be more stable and durable compared to natural biopolymer-based technologies, and the encoded information can be decoded and extracted through specific processes.
Article
Chemistry, Multidisciplinary
Wei-Wei Shi, Chaowei Shi, Tong-Yue Wang, Yu-Lei Li, Yong-Kang Zhou, Xu-Han Zhang, Donald Bierer, Ji-Shen Zheng, Lei Liu
Summary: The chemical synthesis of correctly folded proteins with multiple or interchain disulfide bonds was expedited using a removable glycosylation modification (RGM) strategy, which introduces O-linked beta-N-acetylglucosamine (O-GlcNAc) groups to improve folding and can be efficiently removed afterwards.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Yulei Li, Jie Heng, Demeng Sun, Baochang Zhang, Xin Zhang, Yupeng Zheng, Wei-Wei Shi, Tong-Yue Wang, Jiu-Yi Li, Xiaoou Sun, Xiangyu Liu, Ji-Shen Zheng, Brian K. Kobilka, Lei Liu
Summary: This study presents a practical synthesis method for differentially modified, full-length beta(2)AR receptors. The success in preparing a range of homogeneous samples with distinct modification patterns, including a full-length beta(2)AR bearing both monoubiquitination and octaphosphorylation modifications, provides valuable insights into the structure and interactions of beta(2)AR complexes.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Baochang Zhang, Yupeng Zheng, Guochao Chu, Xiangyu Deng, Tongyue Wang, Weiwei Shi, Yongkang Zhou, Shan Tang, Ji-Shen Zheng, Lei Liu
Summary: This article presents a new method called Backbone-Installed Split Intein-Assisted Ligation (BISIAL) for the synthesis of membrane-associated D-proteins. The BISIAL method allows smooth ligation under strongly chaotropic conditions and the removal of ligation scars on the products, enabling the synthesis of challenging Dprotein targets.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Ruichao Ding, Wei-Wei Shi, Ji-Shen Zheng
Summary: We have successfully synthesized a large quantity of d-SortaseA with high purity using a hydrazide ligation strategy. The d-Sortase exhibited full activity towards d-peptides and D/L hybrid proteins, and the ligation efficiency was not affected by the chirality of the C-terminus substrate. This study suggests that d-sortase ligation can be used as a modern ligation method for d-proteins and D/L hybrid proteins, expanding the toolbox for chemical protein synthesis in biotechnology.
Article
Chemistry, Multidisciplinary
Pan Shi, Yanan Zhang, Pei Lv, Wei Fang, Shenglong Ling, Xiaoqi Guo, Dong Li, Sanling Liu, Demeng Sun, Longhua Zhang, Dongsheng Liu, Ji-Shen Zheng, Changlin Tian
CHEMICAL COMMUNICATIONS
(2020)
Article
Chemistry, Multidisciplinary
Jun Liang, Qingyue Gong, Ying Li, Yong Zheng, Ji-Shen Zheng, Changlin Tian, Jia-Bin Li
CHEMICAL COMMUNICATIONS
(2019)
Review
Chemistry, Organic
Chong Zuo, Baochang Zhang, Bingjia Yan, Ji-Shen Zheng
ORGANIC & BIOMOLECULAR CHEMISTRY
(2019)