Article
Chemistry, Analytical
Yaxue Dai, Yongjia Tang, Wenjing Huang, Yue Zhao, Xin Gao, Yueqing Gu
Summary: This study designed novel EpCAM-targeting peptides YQ-S for precise detection of breast cancer. YQ-S2 showed greater binding affinity and ideal biosafety profile, and was chosen to represent YQ-S. By linking with a near-infrared fluorescent dye, the EpCAM-targeting probe YQ-S2-MPA was developed for real-time imaging and fluorescence-guided resection of breast cancer tumors. In vivo experiments showed higher tumor uptake of YQ-S2-MPA compared to SNF-MPA, and successful detection of metastatic lesions. YQ-S2-MPA also performed excellently in surgical navigation studies in preclinical models.
Article
Chemistry, Applied
Jing-Wen Fan, Shao-Hu Xu, Ying Han, Cao-Guo Yan, Qing Wang
Summary: In this study, a protein structure-dependent probe, OTB, was designed for human serum albumin (HSA) with the assistance of molecular simulation. OTB exhibited favorable selective HSA sensitivity and strong HSA binding ability. Interestingly, the WP5-OTB complex, formed by the cationic molecule OTB and water-soluble pillar [5]arene (WP5), showed improved HSA responsiveness and stronger HSA binding ability compared to OTB alone. The WP5-OTB complex self-assembled into a supramolecular fluorescent probe, demonstrating favorable HSA-induced bioimaging property, pH-sensitive drug delivery property, and photodynamic activity.
Article
Chemistry, Analytical
Yingcui Bu, Mengtao Rong, Junjun Wang, Xiaojiao Zhu, Jie Zhang, Lianke Wang, Zhipeng Yu, Yupeng Tian, Hongping Zhou, Yi Xie
Summary: This study developed a novel molecule MO, which can lastingly anchor onto the plasma membrane and reflect membrane damage and heterogeneity by secretion of extracellular vesicles.
ANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Analytical
Wenjing Huang, Li Wang, Hao Zhang, Zhihao Han, Yueqing Gu
Summary: The incidence of prostate cancer has been rapidly increasing, and tumor marker detection is an effective method for early diagnosis and prognosis. H1, a short peptide probe, has high affinity for malignant tumors overexpressing EGFR, making it a promising tool for cancer diagnosis.
SENSORS AND ACTUATORS B-CHEMICAL
(2023)
Article
Chemistry, Applied
Pan Xu, Shixin Zhou, Sergey I. Druzhinin, Holger Schoenherr, Bo Song
Summary: A pH-sensitive fluorescent probe was created through host-guest assembly, and its fluorescence intensity was dependent on the molar ratio of the two components. The probe showed different emission properties at different molar ratios and exhibited pH-responsive fluorescence. This supramolecular probe could discriminate between different cells based on their pH-dependent fluorescence.
Article
Biochemical Research Methods
Pranab Chandra Saha, Tapas Bera, Tanima Chatterjee, Jayeeta Samanta, Arunima Sengupta, Maitree Bhattacharyya, Samit Guha
Summary: In this study, unsymmetrical visible Cy-3 and near-infrared Cy-5 chromophores were designed and synthesized, self-assembling into fluorescent nanotubes in solution and selectively accumulating inside mitochondria of human carcinoma cells. This accumulation led to early apoptosis targeted at malignant mitochondria, which was confirmed by annexin V-FITC/PI apoptosis detection assay.
BIOCONJUGATE CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Denes Szepesi Kovacs, Balazs Chiovini, Dalma Muller, Estilla Zsofia Toth, Anna Fulop, Peter Abranyi-Balogh, Lucia Wittner, Gyorgy Varady, Odon Farkas, Gabor Turczel, Gergely Katona, Balazs Gyorffy, Gyorgy Miklos Keseru, Zoltan Mucsi, Balazs J. Rozsa, Ervin Kovacs
Summary: A novel family of julolidine-containing fluorescent rhodolsequipped with a wide variety of substituents was synthesized using a versatile two-step process. The synthesized compounds were fully characterized and demonstrated excellent fluorescence properties for microscopy imaging. The best candidate was conjugated to the therapeutic antibody trastuzumab through a copper-free strain-promoted azide-alkyne click reaction. The rhodol-labeled antibody was successfully used for in vitro confocal and two-photon microscopy imaging of Her2+ cells.
Article
Chemistry, Organic
Stephen M. Butler, Maria Hountondji, Stuart N. Berry, Jian Tan, Laurence Macia, Katrina A. Jolliffe
Summary: A macrocyclic fluorescent probe has been developed for the detection of citrate, which exhibits a turn-on in fluorescence upon binding through hydrogen-bonding interactions in aqueous solutions. The probe shows minimal interference from other biologically relevant dicarboxylate species. The utility of this probe has been demonstrated through staining of murine splenocytes and flow cytometry analysis, enabling the identification of different basal levels of citrate in immune cell subsets.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Analytical
Xiaoxia Chen, Xingxing Ren, Yuhan Zhu, Ziyan Fan, Lele Zhang, Zhengjie Liu, Ling Dong, Zijuan Hai
Summary: The study focused on the development of two CTB-activated FL/PA probes, demonstrating high sensitivity and spatial resolution in monitoring CTB activity in vivo. HCy-Cit-Val showed superior performance and is envisioned to be suitable for clinical early diagnosis of CTB-related cancer in the near future.
ANALYTICAL CHEMISTRY
(2021)
Article
Chemistry, Organic
Stephen M. Butler, Maria Hountondji, Stuart N. Berry, Jian Tan, Laurence Macia, Katrina A. Jolliffe
Summary: We introduce a macrocyclic fluorescent probe for the detection of citrate, which exhibits a turn-on fluorescence response upon binding and is minimally affected by other biologically relevant dicarboxylate species. The utility of this probe has been demonstrated through staining murine splenocytes and identifying different basal levels of citrate in immune cell subsets using flow cytometry analysis.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
Pragti, Bidyut Kumar Kundu, Shrish Nath Upadhyay, Nilima Sinha, Rakesh Ganguly, Ivo Grabchev, Srimanta Pakhira, Suman Mukhopadhyay
Summary: In this study, four organometallic Ru(II)-arene complexes were designed and synthesized, and it was found that they possess anticancer, antimetastatic, and two-photon cell imaging abilities. These complexes also demonstrate good catalytic activity in the transfer hydrogenation reaction and strong interactions with biological molecules and DNA. Furthermore, the complexes show capabilities to inhibit cell migration and generate intracellular reactive oxygen species in breast cancer cells.
DALTON TRANSACTIONS
(2022)
Article
Chemistry, Medicinal
Jinman Zhong, Jianke Ding, Lei Deng, Ying Xiang, Duoduo Liu, Yanyan Zhang, Xin Chen, Quanxin Yang
Summary: EpCAM-specific aptamers were successfully selected using Cell-SELEX technology and conjugated with GoldMag nanoparticles to create magnetic molecular probes for MRI detection of prostate cancer. The molecular probes showed high affinity to prostate cancer cells and tissues, producing distinct T2WI signal intensity reduction in MRI.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Huaxi Xiao, Fan Yang, Qinlu Lin, Lin Zhang, Shuguo Sun, Wenhua Zhou, Gao-Qiang Liu
Summary: This study successfully created fluorescent isothiocyanate poly-L-lysine starch nanoparticles (FITC-PLL-StNPs) using native broken-rice starch. It was found that FITC-PLL-StNP-200 exhibited higher fluorescence stability and better detecting effect.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Chemistry, Applied
Linlin Yang, Pengli Gu, Beining Li, Junwan Li, Aoxiang Fu, Xianyu Gong, Yanmei Huang, Lixia Xie, Liguo Ji, Nana Ma, Lili Li, Guangjie He
Summary: Biothiols, such as Hcy, play a crucial role in cell protein metabolism and signal transduction, and are closely associated with various diseases. However, the selective detection of Hcy is still challenging due to its structural similarity to Cys. In this study, a novel fluorescent probe TCF-SBD was developed to selectively detect and visualize Hcy in living cells, showing high sensitivity and selectivity.
Article
Chemistry, Physical
Guang Yu, Yujia Cheng, Zhuohua Duan
Summary: Carbon dots, as novel fluorescent nanomaterials, have gained significant research attention for their simple synthesis, robust fluorescence, low toxicity, and easy functionalization. This study successfully prepared nitrogen-doped yellow fluorescent nano-carbon dots (Y-CDs) with high quantum yield and photostability. The Y-CDs demonstrated effective cobalamin detection and were used as imaging probes for MDA-MB-231 cells.
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
Alexander A. Vinogradov, Jun Shi Chang, Hiroyasu Onaka, Yuki Goto, Hiroaki Suga
Summary: This study reports an integrated platform for accurate profiling of substrate preferences for PTM enzymes. The platform combines mRNA display with next-generation sequencing for high-throughput data acquisition and utilizes deep learning for data analysis. The constructed deep learning models enable comprehensive analysis of enzymatic substrate preferences, quantification of fitness across sequence space, mapping of modification sites, and identification of important amino acids in the substrate. The study demonstrates the complexity of enzymatic preferences and highlights the potential of the developed platform for wider studies of PTM enzymes.
ACS CENTRAL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
R. H. P. van Neer, P. K. Dranchak, L. Liu, M. Aitha, B. Queme, H. Kimura, T. Katoh, K. P. Battaile, S. Lovell, J. Inglese, H. Suga
Summary: By reconfiguring the structure of tRNA, we have successfully incorporated N-methylated amino acids into peptide chains. By utilizing RaPID display technology, we have identified N-methylated macrocyclic peptides with potential bioactivity and conducted structural and functional studies.
ACS CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Physical
Yuchen Zhang, Keisuke Hamada, Dinh Thanh Nguyen, Sumika Inoue, Masayuki Satake, Shunsuke Kobayashi, Chikako Okada, Kazuhiro Ogata, Masahiro Okada, Toru Sengoku, Yuki Goto, Hiroaki Suga
Summary: This study reports a new prenyltransferase, LimF, which geranylates the electron-deficient C2 atom of His imidazole and modifies diverse exotic peptides. Crystallographic analysis provides structural insights into the bifunctionality of LimF and its recognition of substrates. Moreover, the study shows the prenylation ability of LimF on various bioactive molecules containing an imidazole group.
Article
Chemistry, Multidisciplinary
Alexander A. Vinogradov, Yue Zhang, Keisuke Hamada, Jun Shi Chang, Chikako Okada, Hirotaka Nishimura, Naohiro Terasaka, Yuki Goto, Kazuhiro Ogata, Toru Sengoku, Hiroyasu Onaka, Hiroaki Suga
Summary: This study presents a new bioengineering approach for discovering pseudo-natural thiopeptides with favorable pharmacological properties, which was successfully utilized in affinity selection against TNIK kinase, resulting in the discovery of multiple candidate thiopeptides.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Tomohiro Kuroda, Yichao Huang, Soichiro Nishio, Yuki Goto, Hiroaki Suga
Summary: This study reports a new method for the in vitro synthesis of natural-product-like peptides bearing Hhc units. The method incorporates azide/hydroxy acids into the nascent peptide chain through genetic code reprogramming, allowing for the one-pot ribosomal synthesis of designer macrocycles with various Hhc units.
Article
Chemistry, Organic
Yue Zhang, Alexander A. Vinogradov, Jun Shi Chang, Yuki Goto, Hiroaki Suga
Summary: This article presents a strategy for synthesizing novel lactazole-like thiopeptides, including the preparation of central triheterocyclic amino acid and its use in solid-phase peptide synthesis, as well as a technique for preparing C-terminally functionalized thiopeptides for biological studies. The synthesis of 11 TNIK-inhibitor thiopeptides and 6 derivatives highlights the practicality of the developed protocols.
Article
Biology
Takayuki Katoh, Hiroaki Suga
Summary: It has been found that the incorporation of d-alpha-amino acids and N-methyl-l-alpha-amino acids with negatively charged sidechains into nascent peptides is less efficient compared to those with neutral or positively charged ones. This is due to the low binding affinity of their aminoacyl-tRNA to EF-Tu, a translation factor. To overcome this issue, two strategies were adopted: the use of an EF-Tu variant called EF-Sep and reinforcement of T-stem affinity using a chimeric tRNA. These strategies successfully enhanced the incorporation efficiencies of the negatively charged amino acids and demonstrated ribosomal synthesis of macrocyclic peptides containing multiple d-Asp or (Me)Asp.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(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.
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
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
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)
