Article
Chemistry, Multidisciplinary
Masanobu Nagano, Yichao Huang, Richard Obexer, Hiroaki Suga
Summary: This study presents a one-pot ribosomal synthesis method for the construction of macrocyclic depsipeptides, based on the SPCG motif. The ribosomal synthesis of linear peptides containing the SPCG motif with a backbone acyl donor thioester results in spontaneous conversion to corresponding cyclic depsipeptides.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Review
Chemistry, Multidisciplinary
Shay Laps, Gandhesiri Satish, Ashraf Brik
Summary: This review highlights the use of transition metals in the chemical synthesis of peptides and proteins, focusing on recent developments in this exciting research area.
CHEMICAL SOCIETY REVIEWS
(2021)
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
Rebecca Notis Dardashti, Shay Laps, Jacob S. Gichtin, Norman Metanis
Summary: Human selenoprotein H, the only selenocysteine-containing protein located in the cell's nucleolus, is suggested to be involved in DNA binding, reactive oxygen species consumption, and cancer prevention. In this study, a semi-synthetic approach was used to obtain a mutated selenoprotein H and it was demonstrated to have sub-micromolar affinity for DNA binding using biolayer interferometry. The developed semi-synthetic approach can be applied for producing biologically and therapeutically relevant proteins.
Review
Chemistry, Applied
Hisashi Masui, Shinichiro Fuse
Summary: Peptides have gained increasing importance as drugs and drug candidates. Microflow synthesis, with an inner tube diameter of <=1 mm, offers advantages such as precise control of reaction time and temperature, as well as easy scale-up. The combination of microflow technology, automated synthesis, and online monitoring has improved synthetic efficiency and provided reliable data for machine learning models.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2022)
Review
Chemistry, Multidisciplinary
Mohan Kumar, Neelesh C. Reddy, Vishal Rai
Summary: Proteins play a crucial role in monitoring and regulating biological processes, making precise modification tools essential. The establishment of core principles such as chemoselectivity, site-selectivity, and protein-specificity is key in addressing challenges at the intersection of chemistry, biology, and medicine. These principles provide a technological platform for systematically regulating parameters and overcoming various challenges in the field.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Organic
Christopher Berube, Alexandre Borgia, Normand Voyer
Summary: We report the first total synthesis of the macrocyclic decapeptide stylopeptide II, which was achieved using an efficient methodology with oxime resin as solid support. The synthesis was performed at gram-scale without the generation of any detectable undesired side products, demonstrating the general applicability and large-scale synthesis acceleration of this method.
TETRAHEDRON LETTERS
(2022)
Article
Chemistry, Organic
Abigail N. Smith, Jeffrey N. Johnston
Summary: The reinvestigation into the macrocyclooligomerization (MCO) of a tetradepsipeptide revealed a paradox where the MCO of depsipeptide monomers could result in impossible ring sizes, leading to unexpected findings of 18- and 30-membered cyclic oligomeric depsipeptides (CODs). An alternative method for preparing authentic 18- and 36-membered macrocycles was reported, providing definitive analytical characterization for each ring size. The study also included recharacterization and reassignment of two macrocycles originally reported in the MCO series, along with updated data on yields and isothermal titration calorimetry after the implementation of new critical protocols.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Magdalena Wierzbicka, Mateusz Waliczek, Anna Dziadecka, Piotr Stefanowicz
Summary: A one-pot method for peptide cleavage and cyclization from a solid support has been developed, demonstrating feasibility through the synthesis of model short peptides. The entire peptide precursor synthesis can be fully automated without epimerization or dimerization.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Zachary L. Budimir, Rishi S. Patel, Alyssa Eggly, Claudia N. Evans, Hannah M. Rondon-Cordero, Jessica J. Adams, Chittaranjan Das, Elizabeth I. Parkinson
Summary: Macrocyclic peptides show great potential as chemical tools and potential therapeutics. However, their synthesis is currently challenging. In this study, Ulm16, a peptide cyclase belonging to the penicillin-binding protein-type class of thioesterases, is characterized for its ability to catalyze head-to-tail macrolactamization of nonribosomal peptides of 4-6 amino acids in length.
NATURE CHEMICAL BIOLOGY
(2023)
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)
Review
Chemistry, Multidisciplinary
Hichem Moulahoum, Faezeh Ghorbanizamani, Kerem Tok, Figen Zihnioglu
Summary: Peptides are important biomolecules with various applications. However, they have limitations such as flexible conformations and susceptibility to degradation. The discovery of cyclic peptides in plants has provided new insights for overcoming these issues.
Article
Agriculture, Multidisciplinary
Wei Zhang, Natasha T. Forester, Pranav Chettri, Maurice Heilijgers, Wade J. Mace, Evelyne Maes, Yulia Morozova, Emma R. Applegate, Richard D. Johnson, Linda J. Johnson
Summary: The study reveals that the grass-induced Epichloecyclins in Epichloe spp. are ribosomally synthesized and post-translationally modified peptides. Four clustered and coregulated genes, gigA, gigB, gigC, and kexB, are involved in epichloecyclin production. GigB is associated with cyclization, GigC is responsible for N-methylation, and KexB is involved in propeptide cleavage. Disrupting epichloecyclin biosynthesis has little influence on the biosynthesis of E. festucae-associated alkaloids.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Chemistry, Organic
Pak-Lun Lam, Yue Wu, Ka-Leung Wong
Summary: Fmoc-Dab(Mtt)-OH has poor coupling efficiency and undergoes rapid lactamization during solid-phase peptide synthesis. A multi-time and preincubation-free protocol using the coupling reagent DEPBT can achieve complete incorporation, but alternative building blocks are recommended to avoid this costly and tedious procedure.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
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
Biochemistry & Molecular Biology
Carina Hey Pui Cheung, Hoi Yee Chow, Can Li, Pilar Blasco, Kaichao Chen, Sheng Chen, Xuechen Li
Summary: In this study, we report a method for the synthesis of a thiolactone analogue and investigate the reaction conditions for optimal results. The developed protocol can be used for the synthesis of other challenging thiolactone peptides.
Article
Biochemistry & Molecular Biology
Hoi Yee Chow, Kathy Hiu Laam Po, Sheng Chen, Xuechen Li
Summary: This study reports the synthesis and antibacterial evaluation of a series of daptomycin lactam-based analogues. The results show that a daptomycin analogue with singly modified lactam has a significantly higher minimum inhibitory concentration against methicillin-resistant Staphylococcus aureus compared to daptomycin. However, incorporating multiple modifications based on previous studies did not improve the antibacterial activity. Instead, replacing the flexible n-decanoyl group with a rigid 4-(phenylethynyl)benzoyl group greatly reduced the antibacterial activity. The inactivity of the lactam analogue with the 4-(phenylethynyl)benzoyl group suggests a deviation from the active conformation. This series of lactam analogues provides insights into the importance of studying the active conformation of daptomycin and the impact of structural modifications on the active conformation.
JOURNAL OF PEPTIDE SCIENCE
(2022)
Article
Chemistry, Multidisciplinary
Hongxiang Wu, Tongyao Wei, Wai Lok Ngai, Haiyan Zhou, Xuechen Li
Summary: This study developed a new synthesis strategy called LEAD for the synthesis of difficult-to-obtain proteins. The strategy effectively disrupts peptide aggregation by generating specific aldehyde compounds, addressing the challenges of aggregable or colloidal peptide segments in solid-phase peptide synthesis and peptide ligation. The effectiveness of this strategy has been demonstrated through the total syntheses of two proteins.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
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
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
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, Medicinal
Hua-Rui Gong, Ye-fan Hu, Xuechen Li, Thomas Yau, Bao-Zhong Zhang, Jian-Dong Huang
Summary: This study investigates the infection enhancement effect of a multiple epitope-based vaccine on the Omicron strain of SARS-CoV-2. The results show that while the vaccine enhances infection for Omicron, it does not have the same effect on the ancestral SARS-CoV-2 or Delta strains. Furthermore, the study identifies a conserved epitope that has neutralizing activity against the three strains. This research provides up-to-date epitope information for guiding the development of better vaccines or antibody-based therapies against future variants.
ACS INFECTIOUS DISEASES
(2022)
Article
Chemistry, Organic
Yue Zhang, Ruijuan Yin, Hao Jiang, Chaoming Wang, Xiao Wang, Dongping Wang, Kai Zhang, Rilei Yu, Xuechen Li, Tao Jiang
Summary: In this study, a new method for peptide stapling using bifunctional triazine moieties was developed. This method efficiently stabilizes unprotected peptides by conjugating to the phenolic hydroxyl groups of tyrosine. The application of this method to the RGD peptide, which targets integrins, showed significantly improved plasma stability and integrin-targeting ability.
Article
Biochemical Research Methods
Zhenquan Sun, Tongyao Wei, Yihui Cao, Xuechen Li
Summary: In this paper, a rapid protein desulfurization protocol in combination with native chemical ligation is presented for the facile synthesis of proteins with site-specific modifications. The authors demonstrate the use of sodium tetraethylborate (NaBEt4) for this desulfurization, which can be carried out under ambient conditions without the need for inert atmosphere protection, UV irradiation, heating, or exogenous thiol additives. Specifically, the semisynthesis of serotonylated histone H3 (H3Q5ser) via one-pot ligation desulfurization is detailed. This protocol can be used to synthesize proteins of interest with homogeneous post-translational modifications.
Article
Chemistry, Multidisciplinary
Hongxiang Wu, Zhenquan Sun, Xuechen Li
Summary: In this study, we introduced N,O-benzylidene acetal dipeptides (NBDs) as robust and effective building blocks for the direct synthesis of difficult peptides and proteins. The versatility of NBDs was demonstrated in the successful synthesis of various challenging peptides and proteins, including chemokine, therapeutic hormones, histone, and glycosylated erythropoietin.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Biochemistry & Molecular Biology
Wenjie Ma, Han Liu, Xuechen Li
Summary: S-palmitoylation and O-acetylation are two base-labile post-translational modifications (PTMs) in cells. The lability of these PTMs makes their synthesis challenging. This review summarizes the efforts towards the preparation of S-palmitoyl and O-acetyl modified peptides/proteins in the past 40 years, focusing on the evolution of synthetic methods.
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)
Review
Chemistry, Multidisciplinary
Ned P. Buijs, Eilidh J. Matheson, Stephen A. Cochrane, Nathaniel I. Martin
Summary: Since the discovery of penicillin by Fleming, numerous natural product antibiotics have been found, many of which are still clinically important today. These antibiotics selectively target and kill bacterial cells through various mechanisms of action. Bacterial cell wall biosynthesis is a crucial process for their growth and survival, and the vulnerability in maintaining the cell wall is exploited by many antibiotics. In this feature article, we provide an overview of natural product antibiotics that specifically function by binding to membrane-anchored bacterial cell wall precursors.
CHEMICAL COMMUNICATIONS
(2023)