Article
Biochemistry & Molecular Biology
Anpeng Li, Xiang Li, Jihua Zou, Xiaobin Zhuo, Shuai Chen, Xiaoyun Chai, Conghao Gai, Weiheng Xu, Qingjie Zhao, Yan Zou
Summary: A series of hydrocarbon-stapled peptides were designed and synthesized to mimic the alpha-helix of SOS1 as pan-Ras inhibitors. Among these peptides, SSOSH-5 showed a well-constrained alpha-helical structure and high affinity for H-Ras binding. Structural modeling analysis confirmed the binding similarity of SSOSH-5 to the parent linear peptide. SSOSH-5 effectively inhibited the proliferation of pan-Ras-mutated cancer cells and induced dose-dependent apoptosis by modulating downstream kinase signaling.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Xiao-Long He, Cheng Wang, You-Wu Wen, Yi-Bing Zhao, Huan Yang, Shan Qian, Lingling Yang, Zhouyu Wang
Summary: A highly stereoselective dearomative [3 + 2] cycloaddition between cyclic pyridinium ylides and nitroolefins has been developed, using novel cyclic pyridinium salts as ylide precursors. This protocol offers advantages such as broad substrate scope, mild conditions, high yield, and stereoselectivity, providing a concise and efficient method for the construction of spiro-indolizidine scaffolds.
ORGANIC CHEMISTRY FRONTIERS
(2021)
Article
Biochemical Research Methods
Yuna Nakagawa, Jan Vincent V. Arafiles, Yoshimasa Kawaguchi, Ikuhiko Nakase, Hisaaki Hirose, Shiroh Futaki
Summary: This study modified peptides to induce macropinocytosis in the presence of serum, improving the intracellular delivery efficiency of biofunctional macromolecules and nanoparticles.
BIOCONJUGATE CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Motoharu Hirano, Hidetomo Yokoo, Chihiro Goto, Makoto Oba, Takashi Misawa, Yosuke Demizu
Summary: We have developed cell-penetrating stapled peptides based on the amphipathic antimicrobial peptide magainin 2 for efficient intracellular delivery of nucleic acids such as pDNA, mRNA, and siRNA. The stapled peptide st7-5 and its variant st7-5_R can form stable complexes with nucleic acids and successfully deliver them into cells.
Article
Chemistry, Multidisciplinary
Motoharu Hirano, Hidetomo Yokoo, Chihiro Goto, Makoto Oba, Takashi Misawa, Yosuke Demizu
Summary: We have developed cell-penetrating stapled peptides based on the amphipathic antimicrobial peptide magainin 2 for efficient intracellular delivery of nucleic acids including pDNA, mRNA, and siRNA. The peptide st7-5_R can form stable complexes with these nucleic acids and efficiently deliver them into cells.
Article
Chemistry, Multidisciplinary
Takayuki Miki, Keigo Namii, Kenta Seko, Shota Kakehi, Goshi Moro, Hisakazu Mihara
Summary: Phage display is a widely used technique for discovering peptides that bind to target proteins. This study introduces a new method called 'pattern enrichment analysis' to overcome challenges associated with compositional bias. By comparing sequence datasets from affinity-selected samples and non-selected samples, this method allows for the identification of enriched amino acid residue patterns and facilitates the discovery of peptide sequences and key binding residues. The effectiveness of this method was validated through screening against HDM2 protein and the SARS-CoV-2 spike RBD.
Article
Chemistry, Multidisciplinary
Jennifer R. Pace, Bryan J. Lampkin, Charles Abakah, Adam Moyer, Jiayuan Miao, Kirsten Deprey, Robert A. Cerulli, Yu-Shan Lin, James D. Baleja, David Baker, Joshua A. Kritzer
Summary: This study identified an optimal staple for antiparallel beta-strands using a novel computational strategy, and incorporated it into beta-hairpin peptides to create a unique kinked structure. The stapled hairpins demonstrated high structural stability in aqueous solution, excellent degradation resistance in cell lysates, and cytosolic penetration at micromolar concentrations. They also matched specific kinked hairpin motifs at protein-protein interaction interfaces, suggesting potential as starting points for developing inhibitors of cellular protein-protein interactions.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Manuel G. Ricardo, Emelie E. Reuber, Ling Yao, Jose Danglad-Flores, Martina Delbianco, Peter H. Seeberger
Summary: This article describes the design, synthesis, and characterization of the first stapled oligosaccharides, which increases enzymatic stability and cell penetration by applying the concept of stapling short peptides to oligosaccharides.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Organic
Gopathi Ramu, Bheeshma Geetanjali Kodiripaka, Kalakonda Raga Chaitanya, Bathini Nagendra Babu
Summary: The metal-free domino approach for synthesizing various 8-hydroxy-2,8-dihydroindeno[2,1-c]pyrazoles is characterized by high efficiency, mild reaction conditions, greener solvent, scalability, broad substrate scope, high regioselectivity, and yields.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Carmen Lammi, Enrico M. A. Fassi, Marco Manenti, Marta Brambilla, Maria Conti, Jianqiang Li, Gabriella Roda, Marina Camera, Alessandra Silvani, Giovanni Grazioso
Summary: Proprotein convertase subtilisin/kexin 9 (PCSK9) is a key target for the treatment of hypercholesterolemia and cardiovascular diseases. In this study, we discovered Rim13, a polyimidazole derivative that inhibits the interaction between PCSK9 and LDLR. Through computational design, we optimized the shape of PCSK9/ligand complementarity and identified potent diimidazole derivatives. Compound Dim16 showed improved PCSK9 inhibitory activity and some compounds in this series also showed hypocholesterolemic activity by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Xiangli Guo, Linlin Chen, Lidan Wang, Jingping Geng, Tao Wang, Jixiong Hu, Jason Li, Changbai Liu, Hu Wang
Summary: The study identified a short peptide named P2 with high penetration ability to efficiently enter cells, potentially through the endocytosis pathway. Additionally, P2 peptide showed safety in both cell lines and red blood cells.
Article
Chemistry, Multidisciplinary
Cheyenne J. Christopherson, Nathan R. Paisley, Zhujun Xiao, W. Russ Algar, Zachary M. Hudson
Summary: The newly developed orange/red-emitting polymer dots utilize thermally activated delayed fluorescence technology for time-gated imaging, inspired by the cell invasion mechanism of the HIV TAT protein. Pdots efficiently enter various cell types rapidly while maintaining low cellular toxicity, providing a new approach for live-cell fluorescence imaging.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Medicinal
Yiwei Zhang, Jiabei Guo, Jiongjia Cheng, Zhenghua Zhang, Fenghua Kang, Xiaoxing Wu, Qian Chu
Summary: Therapeutic peptides have revolutionized treatment for many human diseases. In recent decades, stapled helical peptides have made rapid progress in drug discovery. Compared to unstabilized linear peptides, stapled helical peptides have shown superior binding affinity, selectivity, membrane permeability, and metabolic stability, offering exciting potential for targeting challenging protein-protein interfaces. This Perspective summarizes the recent use of high-throughput screening technologies for identifying potent stapled helical peptides with optimized binding properties, aiming to accelerate the development of stapled helical peptides as the next generation of therapeutic peptides for various human diseases.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Microbiology
Monika Wojciechowska, Julia Macyszyn, Joanna Miszkiewicz, Renata Grzela, Joanna Trylska
Summary: Anoplin is a promising antimicrobial peptide, and its bactericidal properties can be enhanced by introducing hydrocarbon staples, with changes in charge and position affecting the peptide's destructive activity on the cell wall and thus its antibacterial activity.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Chemistry, Applied
Weihua Jin, Chenghui Lu, Yanan Zhu, Jing Zhao, Wenjing Zhang, Lianchun Wang, Robert J. Linhardt, Chunyu Wang, Fuming Zhang
Summary: Tau spreading in Alzheimer's disease is mediated by cell surface heparan sulfate (HS). Fucoidans, a class of sulfated polysaccharides, can compete with HS to bind tau and inhibit tau spreading. Two fractions of fucoidans, sulfated galactofucan (SJ-I) and sulfated heteropolysaccharide (SJ-GX-3), exhibited strong binding abilities and inhibited tau-cell interaction and tau cellular uptake.
CARBOHYDRATE POLYMERS
(2023)
Article
Biochemical Research Methods
Avinash Muppidi, Sang Jun Lee, Che-Hsiung Hsu, Huafei Zou, Candy Lee, Elsa Pflimlin, Madhupriya Mahankali, Pengyu Yang, Elizabeth Chao, Insha Ahmad, Andreas Crameri, Danling Wang, Ashley Woods, Weijun Shen
BIOCONJUGATE CHEMISTRY
(2019)
Article
Biochemistry & Molecular Biology
Andrew E. Lin, Qing Lin
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Article
Chemistry, Organic
Yulin Tian, Huafei Zou, Peng An, Zhihong Zhou, Weijun Shen, Qing Lin
Article
Biochemistry & Molecular Biology
Yulin Tian, Qing Lin
ACS CHEMICAL BIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Yulin Tian, Ming Fang, Qing Lin
Summary: The intracellular fluorescent labeling of GCGR ICL3 using a bioorthogonal chemistry strategy was achieved successfully, but faced challenges in live-cell imaging studies due to the interference of specific and non-specific signals. Further research is needed to overcome these challenges and improve the specificity of the labeling reactions.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Gangam Srikanth Kumar, Stefano Racioppi, Eva Zurek, Qing Lin
Summary: This article reports the design of a super fast bioorthogonal ligation reactant pair, enabling rapid bioorthogonal labeling on live cells.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Yifang Yang, Candy Lee, Reddy Rajasekhar Reddy, David J. Huang, Weixia Zhong, Van T. B. Nguyen-Tran, Weijun Shen, Qing Lin
Summary: Recent trials have demonstrated that chimeric peptides activating GLP-1R and GIPR simultaneously are more effective in glycemic control and weight reduction than those activating GLP-1R alone. However, linear peptide-based dual agonists are not suitable for oral administration due to susceptibility to proteolytic cleavage. This study presents the design and synthesis of biaryl-stapled peptides with improved proteolytic stability. These stapled peptides showed strong dual agonist activities and exhibited excellent efficacy in an oral glucose tolerance test in mice.
ACS CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Yali Xu, Abdur Rahim, Qing Lin
Summary: In this study, we designed N-2-carboxy-4-aryl-1,2,3-triazole-lysines (CATKs) and incorporated them into proteins via genetic code expansion. CATKs allowed for spontaneous, site-selective crosslinking to generate covalent protein dimers in living cells. The resulting crosslinked proteins showed improved cellular uptake and enhanced stability.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Gangam Srikanth Kumar, Qing Lin
Summary: Fast bioorthogonal reactions have superior performance in labeling low-abundance biomolecules in native cellular environments. Photochemically activated nitrile imine and tetrazine intermediates have been successfully used for efficient bioorthogonal labeling of biomolecules in live cells.
Article
Chemistry, Multidisciplinary
Zheng Wang, Johnathan D. Rabb, Qing Lin
Summary: Compared to disulfide bonds, little attention has been given to naturally occurring intramolecular crosslinks, mainly due to their rarity in proteins. This article presents examples of natural non-disulfide crosslinks, known as orthogonal crosslinks, and highlights their impact on protein topology and function. Recent efforts to expand orthogonal crosslinks by utilizing protein circularization enzymes or the genetic code expansion strategy are summarized, including the advantages, disadvantages, and applications in generating novel protein topology and function. The spontaneous orthogonal crosslinking using a carbamate-based crosslink and its applications in designing topology-mimicking bacterial adhesins are specifically emphasized.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Ming Fang, Gangam Srikanth Kumar, Qing Lin
Summary: This study reports the synthesis of hydrazonyl sultones (HS) with an ortho-CF3 group and different N-aryl substituents, and investigates their stability and reactivity towards BCN in a 1,3-dipolar cycloaddition reaction. The HS show good aqueous stability due to the electrostatic shielding effect of the CF3 group. The N-aryl substituents further influence the reactivity and stability of the HS, with electron-rich six-membered HS demonstrating excellent stability and increased cycloaddition reactivity. These improved HS reagents enable fast and selective modification of BCNK-encoded nanobodies.
Article
Chemistry, Multidisciplinary
Ming Fang, Gangam Srikanth Kumar, Stefano Racioppi, Heyang Zhang, Johnathan D. Rabb, Eva Zurek, Qing Lin
Summary: In this study, a new class of bioorthogonal reagents called hydrazonyl sultones (HS) were designed and synthesized as stable tautomers of highly reactive nitrile imines (NI). The HS demonstrated broad aqueous stability and tunable reactivity in a 1,3-dipolar cycloaddition reaction, depending on substituents, sultone ring structure, and solvent conditions. DFT calculations provided insights into the HS -> NI tautomerism and comparative kinetic analysis revealed the extraordinary stability of HS. The utility of HS was demonstrated in selective modification of nanobodies and fluorescent labeling of a transmembrane glucagon receptor.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Tracey M. Lewandowski, Peng An, Carlo P. Ramil, Ming Fang, Qing Lin
Summary: This study presents an integrated approach combining enzymatic SNAP-tagging and bioorthogonal chemistry for dual fluorescent labeling of GLP-1R. The resulting GLP-1R conformational biosensors enable FRET-based analysis of the receptor subdomain movement in response to ligand stimulation in live cells.
RSC CHEMICAL BIOLOGY
(2022)
Review
Chemistry, Multidisciplinary
Gangam Srikanth Kumar, Qing Lin
Summary: The merger of click chemistry with discrete photochemical processes has given rise to a new class of reactions known as photoclick chemistry, allowing for rapid and precise synthesis of organic structures under mild conditions. Photoclick chemistry provides unparalleled control over reactive intermediate generation, making it indispensable in spatially addressable applications such as biomolecular labeling and polymer conjugation. Particularly popular are photoclick reactions based on 1,3-dipolar cycloadditions and Diels-Alder reactions due to their excellent reaction kinetics, selectivity, and biocompatibility.
Article
Multidisciplinary Sciences
Samuel L. Scinto, Didier A. Bilodeau, Robert Hincapie, Wankyu Lee, Sean S. Nguyen, Minghao Xu, Christopher W. Am Ende, M. G. Finn, Kathrin Lang, Qing Lin, John Paul Pezacki, Jennifer A. Prescher, Marc S. Robillard, Joseph M. Fox
Summary: Bioorthogonal chemistry involves high-yielding chemical reactions in biological environments that are rapid and selective, playing essential roles in various fields such as biomedical imaging and drug delivery. Its applications are diverse and include genetic code expansion, drug target identification, and antibody-drug conjugation.
NATURE REVIEWS METHODS PRIMERS
(2021)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
