Article
Chemistry, Medicinal
Xinting Li, Timothy W. Craven, Paul M. Levine
Summary: Cyclic peptides, with their diverse architectures, show potential in intervening and regulating challenging targets. Various screening technologies can be used to generate cyclic peptide libraries for drug research in modern medicine.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
G. Pepe, R. Appierdo, C. Carrino, F. Ballesio, M. Helmer-Citterich, P. F. Gherardini
Summary: Understanding the interactions between RNA molecules and proteins or other molecules is a major challenge in biology. This review summarizes recent computational methods for predicting RNA-RNA or RNA-protein interactions, focusing on feature encoding and machine learning strategies. It also explores the impact of dataset size and quality on performance and discusses approaches for generating negative example datasets for training. Additionally, it describes the best-performing methods for predicting interactions between proteins and specific classes of RNA molecules and methods for predicting RNA-RNA or RNA-RBP interactions independently of the RNA type.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Sebastian Dengler, Ryan T. Howard, Vasily Morozov, Christos Tsiamantas, Wei-En Huang, Zhiwei Liu, Christopher Dobrzanski, Vojislava Pophristic, Sophie Brameyer, Celine Douat, Hiroaki Suga, Ivan Huc
Summary: Expanding the chemical diversity of peptide macrocycle libraries through the inclusion of a large aromatic helical foldamer has been implemented. A hybrid macrocyclic nanomolar binder to the C-lobe of the E6AP HECT domain was selected, and its crystal structure and molecular dynamics simulations revealed an intriguing reciprocal helical folding of the peptide and foldamer. The results represent a significant extension in the chemical space amenable to display selection and highlight the potential benefits of incorporating an aromatic foldamer into a peptide macrocycle for protein recognition.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Engineering, Biomedical
Jiang Le, Liu Zhongqun, Wang Zhaoyan, Su Yijun, Wang Yingjin, Wei Yaojie, Jiang Yanan, Jia Zhanrong, Ma Chunyang, Gang Fangli, Xu Nan, Zhao Lingyun, Wang Xiumei, Wu Qiong, Lu Xiong, Sun Xiaodan
Summary: The fate of mesenchymal stem cells (MSCs) can be regulated by biological, physical, and chemical signals, with advancements in high-throughput technology playing a crucial role in monitoring and understanding these regulations. Future research should focus on designing and synthesizing better bone bioactive materials (BBMs) that can accurately control the fate of MSCs.
BIOACTIVE MATERIALS
(2021)
Article
Multidisciplinary Sciences
Assaf Alon, Jiankun Lyu, Joao M. Braz, Tia A. Tummino, Veronica Craik, Matthew J. O'Meara, Chase M. Webb, Dmytro S. Radchenko, Yurii S. Moroz, Xi-Ping Huang, Yongfeng Liu, Bryan L. Roth, John J. Irwin, Allan Basbaum, Brian K. Shoichet, Andrew C. Kruse
Summary: The study determined the crystal structure of sigma(2) receptor with roluperidone and PB28, identified new chemical compounds with higher affinities, and confirmed the role of sigma(2) receptor in pain perception, highlighting the potential for developing new pain treatments.
Article
Chemistry, Multidisciplinary
Qichao Yao, Jiangli Fan, Saran Long, Xueze Zhao, Haidong Li, Jianjun Du, Kun Shao, Xiaojun Peng
Summary: Conventional photodynamic therapy is hindered by the hypoxic environment of solid tumors, but novel photosensitizer NBEX (X = S, Se, Te) can destroy RNA in cancer cells without oxygen and accumulate in tumor area quickly.
Article
Microbiology
Chenglong Ma, Chunyang Jiang, Dongping Zhao, Shuhao Li, Ronggui Li, Lei Li
Summary: Directed evolution is a widely-used engineering strategy for improving protein stability or biochemical functions through repeated rounds of mutation and selection. Using ELISA to check the displayed protein against the target and enhancing the signal through various approaches can improve the sensitivity of ELISA experiments when dealing with low-affinity ligand-protein interactions.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Sharon Min Qi Chee, Jantana Wongsantichon, Lau Sze Yi, Barindra Sana, Yuri Frosi, Robert C. Robinson, Farid J. Ghadessy
Summary: This study demonstrates the use of vGFP as a scaffold for displaying peptides, showing that peptides correctly inserted in the linker region can interact with targets both in vitro and in live cells. The thermostable and inherently fluorescent properties of vGFP make it a promising tool for disrupting clinically relevant protein-protein interactions.
SCIENTIFIC REPORTS
(2021)
Review
Chemistry, Multidisciplinary
Wai Cheung Chan, Shabnam Sharifzadeh, Sara J. Buhrlage, Jarrod A. Marto
Summary: Covalent drugs are essential in modern medicine, and there has been a recent surge in interest in the development of covalent inhibitors, particularly utilizing mass spectrometry-based chemoproteomic methods. This review highlights the practical applications of these techniques in target identification, hit discovery, and lead characterization/optimization in covalent drug discovery, with case studies to demonstrate their real-world significance and future opportunities.
CHEMICAL SOCIETY REVIEWS
(2021)
Article
Chemistry, Multidisciplinary
Jun Shi Chang, Alexander A. Vinogradov, Yue Zhang, Yuki Goto, Hiroaki Suga
Summary: A deep learning model was used to streamline the design of mRNA display libraries, leading to the discovery of potent thiopeptide ligands with favorable pharmacological properties against IRAK4 kinase and TLR10 cell surface receptor.
ACS CENTRAL SCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Mengmeng Zheng, Fa-Jie Chen, Kaicheng Li, Rahi M. Reja, Fredrik Haeffner, Jianmin Gao
Summary: Binding via reversible covalent bond formation is a powerful mechanism to enhance the potency of synthetic inhibitors. This study reports the development of chemically modified phage libraries that incorporate 2-acetylphenylboronic acid (APBA) for reversible binding, and demonstrates their utility against two protein targets, showing high potency and specificity.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Review
Pharmacology & Pharmacy
Mei-Yue Wang, Rong Zhao, Yu-Lan Wang, De-Ping Wang, Ji-Min Cao
Summary: This review provides an overview of the biology of flaviviruses and the current advances in RNA-based therapeutics for them. The authors also discuss the challenges and possible solutions in this area. They emphasize the importance of maintaining the current momentum in the development of safe and effective anti-flavivirus drugs through joint efforts of academia, government, and industry.
EXPERT OPINION ON DRUG DISCOVERY
(2023)
Review
Genetics & Heredity
Ravi Tharakan, Akira Sawa
Summary: A novel class of small proteins called micropeptides, shorter than 100 amino acids, have been found to play important roles in physiological and cellular systems. Ongoing research is focused on discovering and characterizing more micropeptides using -omics methods such as proteomics, RNA sequencing, and ribosome profiling. Future endeavors in the micropeptide field will face methodological and conceptual challenges.
FRONTIERS IN GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Samantha Nelson, Timothy J. Harris, Christine S. Muli, Marianne E. Maresh, Braden Baker, Chloe Smith, Chris Neumann, Darci J. Trader, Elizabeth I. Parkinson
Summary: In this study, cyclic peptide proteasome stimulators (CyPPSs) were discovered as chemical tools capable of stimulating the proteasome and enhancing clearance of misfolded proteins. This finding provides strong support for proteasome stimulation as a therapeutic strategy for neurodegenerative diseases.
Review
Pharmacology & Pharmacy
Hai Tao Xue, Michael Stanley-Baker, Adams Wai Kin Kong, Hoi Leung Li, Wilson Wen Bin Goh
Summary: Natural products are a valuable resource for drug development, but analyzing their complex data is a challenge. Artificial intelligence techniques can help overcome this limitation. However, further work is needed in knowledge and resource development, as well as modeling considerations, limitations, and challenges.
DRUG DISCOVERY TODAY
(2022)
Article
Chemistry, Multidisciplinary
Takayuki Katoh, Hiroaki Suga
Summary: In this study, we have successfully overcome the challenge of ribosomal elongation of aromatic cyclic beta(2,3)-amino acids and discovered potent binding peptides against human IFNGR1 and FXIIa. These peptides not only exhibit high inhibitory activity but also demonstrate high protease resistance in human serum.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Kenya Tajima, Takayuki Katoh, Hiroaki Suga
Summary: High concentration of EF-G triggers the mistranslocation of tRNAs in ribosomal translation, leading to inefficient peptide synthesis and truncated peptides. This event can be alleviated by reinitiating peptide synthesis. Reinitiated peptides during ribosomal translation can accumulate in cells.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Matthew G. Alteen, Hayden Peacock, Richard W. Meek, Jil A. Busmann, Sha Zhu, Gideon J. Davies, Hiroaki Suga, David J. Vocadlo
Summary: This study applied an mRNA display technology with genetic code reprogramming to identify macrocyclic peptides that can inhibit O-GlcNAc transferase (OGT) activity. These macrocycles bind to the tetratricopeptide repeats of OGT and inhibit its activity through an allosteric mechanism. The high potency and novel mechanism of action of these OGT ligands may contribute to further understanding the specificity and regulation of OGT.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Takahiro Ono, Kazuhito V. Tabata, Yuki Goto, Yutaro Saito, Hiroaki Suga, Hiroyuki Noji, Jumpei Morimoto, Shinsuke Sando
Summary: Cyclic peptides that passively penetrate cell membranes are being actively researched in drug discovery. Common methods like PAMPA and Caco-2 assay have limitations in accurately measuring their permeability. A new lipid bilayer permeability assay was developed for label-free measurements of cyclic peptide permeability.
Review
Chemistry, Multidisciplinary
Abhishek Saha, Hiroaki Suga, Ashraf Brik
Summary: Chemical manipulation of naturally occurring peptides offers a convenient route for generating analogs to screen different therapeutic targets. mRNA display provides advantages in terms of library size and the recovery of selected polypeptide sequences.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Article
Medicine, Research & Experimental
Shota Warashina, Hiroki Sato, Maki Zouda, Maiko Takahashi, Yasuhiro Wada, Toby Passioura, Hiroaki Suga, Yasuyoshi Watanabe, Kunio Matsumoto, Hidefumi Mukai
Summary: In this study, Cu-64-labeled HiP-8 molecules were synthesized and used as PET probes in human HGF knock-in humanized mice. The results showed that Cu-64-labeled HiP-8 probes are suitable for tcHGF imaging in vivo, and secretory proteins like tcHGF can be a target for PET imaging.
MOLECULAR PHARMACEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Takayuki Katoh, Hiroaki Suga
Summary: Using a chimeric initiator tRNA and EF-P can effectively suppress the N-terminal drop-off event induced by noncanonical initiator substrates, leading to the synthesis of full-length peptides. By optimizing translation conditions, complete suppression of exotic amino acids and up to a 1000-fold increase in expression level of full-length peptides can be achieved.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Xiao Ma, Marina Bakhtina, Irina Shulgina, William A. Cantara, Alexandra B. Kuzmishin Nagy, Yuki Goto, Hiroaki Suga, Mark P. Foster, Karin Musier-Forsyth
Summary: High fidelity tRNA aminoacylation is crucial for cell viability. ProXp-ala, a trans-editing protein, hydrolyzes mischarged Ala-tRNA(Pro) and prevents mistranslation of proline codons. This study reveals the structural basis for C1:G72 recognition by ProXp-ala and its potential implications for antibiotic drug design.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Takayuki Katoh, Hiroaki Suga
Summary: In translation initiation in prokaryotes, IF3 recognizes the interaction between the initiator codon of mRNA and the anticodon of fMet-tRNA(ini) and then relocates the fMet-tRNA(ini) to an active position. EF-G and RRF are involved in disassembling an aberrant ribosome complex bearing inactive fMet-tRNA(ini) to alleviate the amino-terminal drop-off-reinitiation caused by unfavorable codon-anticodon combinations with weaker base pairs.
Article
Chemistry, Multidisciplinary
Naoya Kawakami, Hiroki Sato, Naohiro Terasaka, Kunio Matsumoto, Hiroaki Suga
Summary: The researchers have developed a ubiquitin-based protein ligand multimer, called U-bodies, as a surrogate agonist for the MET receptor. These U-body constructs have high binding affinity, thermal stability, and proteolytic stability. By assembling them into dimeric, tetrameric, and octameric structures, potent MET activation and cell proliferation-promoting activities are achieved.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Yuchen Zhang, Keisuke Hamada, Masayuki Satake, Toru Sengoku, Yuki Goto, Hiroaki Suga
Summary: Prenyltransferases in cyanobactin biosynthesis have been engineered to modify their prenylation modes, leading to the discovery of a novel farnesylation mode. The understanding of essential residues for farnesyl-binding pocket construction has allowed for the rational design of additional peptide alkylation biocatalysts.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Takayuki Katoh, Hiroaki Suga
Summary: This study comprehensively analyzed the mapping between amino acids and codons, as well as the pattern of misdecoding. Two rules were revealed regarding the occurrence of misdecoding, and it was found that less diverse amino acids are assigned to codons that induce more frequent misdecoding in order to minimize deleterious effects.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Hongxue Chen, Takayuki Katoh, Hiroaki Suga
Summary: By introducing a membrane penetration motif, peptides exhibit improved membrane permeability. Macrocyclization of peptides closed by a hydrophobic bipyridyl unit improves their membrane permeability and proteolytic stability. The combination of the RaPID system with a hydrophobic unit like BPy provides a potential approach for designing cell penetrating macrocycles.
ACS BIO & MED CHEM AU
(2023)
Article
Multidisciplinary Sciences
Betsegaw Lemma, Di Zhang, Ganga B. Vamisetti, Bryan G. Wentz, Hiroaki Suga, Ashraf Brik, Jacek Lubkowski, David Fushman
Summary: The mechanism of affinity and binding selectivity of cyclic peptides with polyubiquitin chains has been uncovered, along with the requirements for preferential selection of specific structures in longer polyubiquitin chains. These structural insights will guide the development of next-generation cyclic peptides with enhanced anti-cancer activity.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Jun Shi Chang, Alexander A. Vinogradov, Yue Zhang, Yuki Goto, Hiroaki Suga
Summary: A deep learning model was used to streamline the design of mRNA display libraries, leading to the discovery of potent thiopeptide ligands with favorable pharmacological properties against IRAK4 kinase and TLR10 cell surface receptor.
ACS CENTRAL SCIENCE
(2023)