Article
Plant Sciences
Zhenjun Li, Yongsheng Tian, Bo Wang, Rihe Peng, Jing Xu, Xiaoyan Fu, Hongjuan Han, Lijuan Wang, Wenhui Zhang, Yongdong Deng, Yu Wang, Zehao Gong, Jianjie Gao, Quanhong Yao
Summary: This study successfully redirected selenium flow in rice by overexpressing the genes encoding selenocysteine lyase and selenocysteine methyltransferase. Transgenic plants showed lower sensitivity to selenium stress and increased tolerance to selenate and selenite, as well as improved selenium elimination capabilities. These findings suggest that genetically modified plants have the potential to restore selenium-contaminated environments.
JOURNAL OF PLANT PHYSIOLOGY
(2022)
Review
Chemistry, Medicinal
Kainat Ahmed, Ghayoor Abbas Chotana, Amir Faisal, Rahman Shah Zaib Saleem
Summary: This article summarizes the synthetic methodologies of selenium-containing peptides and provides a brief description of their chemistry and biological activities. These methodologies enable the access to various natural and unnatural selenium-containing peptides that have been used in a range of applications, from modulating protein characteristics to structure-activity relationship studies for applications in nutraceuticals and drug development.
MINI-REVIEWS IN MEDICINAL CHEMISTRY
(2023)
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.
Article
Chemistry, Analytical
Huan Tang, Guogeng Jia, Jinjun Gao, Fan Yang, Ziyao Tang, Yuan Liu, Chu Wang
Summary: In this paper, a chemical proteomic strategy called SETRIP was developed to quantitatively monitor the turnover dynamics of selenoproteins at the proteomic level. The half-lives of nine selenoproteins were accurately measured, ranging from 6 to 32 hours. The study provides a global portrait of dynamic changes in the selenoproteome and suggests the existence of hierarchy regulation in the turnover of selenoproteins.
ANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Jing Liu, Youqiao Xu, Haojie Lu, Rong Wang, Zhuolu Xia, Changshun Zhao, Dechun Huang, Feng Jiang, Wei Chen
Summary: Three self-assembled nanoaggregates were constructed using different molecules, and their properties were characterized through various experiments. The results showed that nanoaggregates with disulfide groups exhibited better stability and improved cytotoxicity against cancer cells. Additionally, the nanoaggregates showed targeting ability to specific cellular components, leading to enhanced antitumor efficacy.
Article
Chemistry, Multidisciplinary
Angus S. Mackay, Joshua W. C. Maxwell, Max J. Bedding, Sameer S. Kulkarni, Stephen A. Byrne, Lucas Kambanis, Mihai V. Popescu, Robert S. Paton, Lara R. Malins, Anneliese S. Ashhurst, Leo Corcilius, Richard J. Payne
Summary: This study describes the development of an electrochemical selenoetherification (e-SE) platform for the selective and efficient functionalization of polypeptides under mild conditions. The unique reactivity of selenocysteine allows the formation of stable selenoether-linked conjugates through electrochemical reactions. The utility of this platform is demonstrated through the modification of a FDA-approved cancer drug and the assembly of complex anti-HER2 affibody conjugates. The functionalized affibodies show potential applications in in vitro imaging and targeting of HER2-positive tumor cells.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Didac Santesmasses, Vadim N. Gladyshev
Summary: Through analysis of the co-essentiality network, this study identified functional partners of selenoproteins and Sec machinery proteins. The key role of selenium is to support the functions of GPX4 and TXNRD1, with further functional links to PRDX6 and SCD.
Review
Food Science & Technology
L. Gonzalez-Salitre, Ad Roman-Gutierrez, E. Contreras-Lopez, M. Bautista-Avila, Gm Rodriguez-Serrano, Lg Gonzalez-Olivares
Summary: This article reviews the importance of selenium in the diet and the biochemical mechanism of yeast in transforming inorganic selenium into organic species.
FOOD REVIEWS INTERNATIONAL
(2023)
Article
Chemistry, Applied
Sindija Lapcinska, Pavels Dimitrijevs, Pavel Arsenyan
Summary: A visible light-initiated method has been developed for the preparation of Se-S bond-containing peptides, showing good tolerance, stability, and the ability to serve as an oxidation-sensitive linker.
ADVANCED SYNTHESIS & CATALYSIS
(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
Spectroscopy
Gustavo Moreno-Martin, Elena Espada-Bernabe, Beatriz Gomez-Gomez, Maria Eugenia Leon-Gonzalez, Yolanda Madrid
Summary: This study evaluated the transformations of selenium nanoparticles and selenite in Escherichia coli and Staphylococcus aureus, and found that selenocysteine was the only selenium species identified in both bacteria. Bacterial growth in the presence of selenite resulted in the formation of biogenic selenium nanoparticles.
SPECTROCHIMICA ACTA PART B-ATOMIC SPECTROSCOPY
(2023)
Article
Chemistry, Multidisciplinary
Ogonna Nwajiobi, Ashish Kumar Verma, Monika Raj
Summary: A novel rapid arene triazene strategy for macrocyclization of peptides is reported, which can generate a chromophoric triazene moiety at the site of cyclization within a minute. The resulting triazene cyclic peptide is highly stable but responsive to external stimuli and can undergo ring opening and re-cyclization. This method works with unprotected peptides and has been applied for the synthesis of monocycles and bicycles with various amino acid compositions. The stability of triazene cyclic peptides allows post-cyclization modification. This strategy has important applications in chemical biology, selective drug delivery, and identification of cyclic peptide hits.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Silin Xu, Dandan Jiang, Zejun Peng, Long Hu, Tao Liu, Lili Zhao, Junfeng Zhao
Summary: This article presents a systematic mechanistic analysis of ynamide-mediated peptide bond formation and its application expansion. The study finds that ynamide exhibits superiority in addressing the issue of racemization/epimerization during peptide bond formation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Shaogao Zeng, Songlin Fang, Haiping Cai, Dong Wang, Weiliang Liu, Xinwei Hu, Pinghua Sun, Zhixiong Ruan
Summary: A novel selenium-electrocatalytic intramolecular cyclization has been developed for the synthesis of functionalized indoles and azaindoles. This sustainable method enables broad substrate scope and synthesis of highly functional indoles under mild conditions, using a recyclable selenium catalyst.
CHEMISTRY-AN ASIAN JOURNAL
(2022)
Review
Biochemistry & Molecular Biology
Yan Zhang, Jiao Jin, Biyan Huang, Huimin Ying, Jie He, Liang Jiang
Summary: Selenium is an important trace element that is mainly present as selenocysteine in prokaryotes. It is required for the synthesis of certain nucleotides and cofactors, and participates in redox reactions. Recent advances in bioinformatics analysis have provided insights into the utilization of selenium in prokaryotes, including the identification of selenoprotein genes and comparative genomics studies. These studies have revealed the evolutionary trends of selenium metabolic pathways, selenoprotein families, and selenoproteomes in different organisms and environmental samples.
Article
Chemistry, Multidisciplinary
Patricia Lopez-Garcia, Aline D. de Araujo, Ana E. Bergues-Pupo, Isabell Tunn, David P. Fairlie, Kerstin G. Blank
Summary: Coiled coils can be stabilized and fine-tuned for thermodynamic and mechanical stability by introducing helix-inducing macrocyclic constraints known as staples. The number of staples affects thermodynamic stabilization against helix uncoiling, while the positioning of staples controls mechanical stability of CCs. Different types, positions, and numbers of staples are key design parameters for using helical macrocyclic templates in emerging biomaterials to adjust CC properties.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Pharmacology & Pharmacy
David A. Eagles, Chun Yuen Chow, Glenn F. King
Summary: This review examines the role of Na(V)1.7 channels in nociception, their history as a therapeutic target, and the challenges in developing potent inhibitors. Despite significant progress in drug development, effective analgesia remains elusive in clinical trials.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Markus Muttenthaler, Glenn E. King, David J. Adams, Paul E. Alewood
Summary: This Perspective summarizes key trends in peptide drug discovery and development, including human hormones, elegant medicinal chemistry and rational design strategies, peptide drugs derived from nature, and major breakthroughs in molecular biology and peptide chemistry. It also emphasizes lessons from earlier approaches that are still relevant today and discusses emerging strategies impact on peptide drug discovery.
NATURE REVIEWS DRUG DISCOVERY
(2021)
Article
Chemistry, Multidisciplinary
Aline D. Araujo, Huy N. Hoang, Junxian Lim, Jeffrey Y. W. Mak, David P. Fairlie
Summary: Summary: Aromatic groups play a crucial role in protein-membrane association and cell uptake. The electrostatic and hydrophobic properties of aromatic ring substituents influence the affinity towards phospholipid membranes. The combination of fluorine and sulfur substituents induces microdipoles, enhancing the cell uptake of peptides.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Liping Liu, Richard M. Lucas, Jeffrey D. Nanson, Yan Li, Jason Whitfield, James E. B. Curson, Neeraj Tuladhar, Kirill Alexandrov, Mehdi Mobli, Matthew J. Sweet, Bostjan Kobe, Jennifer L. Stow, Lin Luo
Summary: In this study, we identify a novel immune-specific Syk scaffold protein SCIMP, which can contribute to inflammation through selective TLR-driven inflammatory responses.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Volker Herzig, Yong-Cyuan Chen, Yanni K-Y Chin, Zoltan Dekan, Yu-Wang Chang, Hui-Ming Yu, Paul F. Alewood, Chien-Chang Chen, Glenn F. King
Summary: This study identified a tarantula venom from Avicularia spec. that can inhibit specific subtypes of T-type calcium channels, with the active toxin being omega-Avsp1a. The research suggests that omega-Avsp1a can inhibit specific subtypes of T-type calcium channels, and the domain-1 of Ca(V)3.3 is crucial for this inhibitory effect.
Article
Multidisciplinary Sciences
Biswaranjan Mohanty, Julien Orts, Geqing Wang, Stefan Nebl, Wesam S. Alwan, Bradley C. Doak, Martin L. Williams, Begona Heras, Mehdi Mobli, Martin J. Scanlon
Summary: The structures of protein-ligand complexes are crucial for drug design, and are mainly determined using X-ray crystallography. However, when crystallography fails, NMR is often used as an alternative method. Unfortunately, the tools available for rapid and robust structure determination of protein-ligand complexes by NMR are currently limited. In this study, the NMR2 approach is described, which allows the determination of the binding pose of a small molecule in a weak protein-ligand complex by collecting sparse protein methyl-to-ligand NOEs from a selectively labeled protein sample and an unlabeled ligand. This approach extends the utility of NMR2 to larger protein-ligand complexes.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Fernanda C. Cardoso, Sandy S. Pineda, Volker Herzig, Kartik Sunagar, Naeem Yusuf Shaikh, Ai-Hua Jin, Glenn F. King, Paul F. Alewood, Richard J. Lewis, Sebastien Dutertre
Summary: Australian tree-dwelling funnel-web spiders have venom that induces deadly symptoms and exhibits different venom composition compared to ground-dwelling species. The venom of tree-dwellers strongly modulates human voltage-gated sodium and calcium channels, while also showing potent insecticidal effects. This study contributes to understanding the molecular and pharmacological basis for severe envenomation by Australian tree-dwelling funnel-web spiders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Michael D. Healy, Joanna Sacharz, Kerrie E. McNally, Calum McConville, Vikas A. Tillu, Ryan J. Hall, Molly Chilton, Peter J. Cullen, Mehdi Mobli, Rajesh Ghai, David A. Stroud, Brett M. Collins
Summary: SNX17 controls the endosomal recycling of transmembrane cargo proteins through its association with the Commander trafficking complex and the PDLIM family of proteins. The interaction between SNX17 and PDLIM is mediated by a unique peptide interaction involving electrostatic contacts and a conserved proline-containing loop sequence. This interaction may play a role in regulating the activity of SNX17 in conjunction with Commander and actin-rich endosomal trafficking domains.
Article
Biochemistry & Molecular Biology
Junyu Liu, Michael Maxwell, Thom Cuddihy, Theo Crawford, Madeline Bassetti, Cameron Hyde, Steve Peigneur, Jan Tytgat, Eivind A. B. Undheim, Mehdi Mobli
Summary: Receptor avidity through multivalency is difficult to engineer in synthetic molecules, but can be found in natural bivalent antibodies. The discovery of bivalent venom peptides with tandem repeat domains has provided insight into multivalency in biomolecules. ScrepYard, an online resource, assists in identifying SCREP sequences and characterizing this emerging class of biomolecules.
Article
Biochemical Research Methods
Qiushi Cao, Cheng Ge, Xuejie Wang, Peta J. Harvey, Zixuan Zhang, Yuan Ma, Xianghong Wang, Xinying Jia, Mehdi Mobli, David J. Craik, Tao Jiang, Jinbo Yang, Zhiqiang Wei, Yan Wang, Shan Chang, Rilei Yu
Summary: With the rise of multidrug-resistant bacteria, antimicrobial peptides (AMPs) have emerged as potential alternatives to traditional antibiotics for treating bacterial infections. However, traditional methods of discovering and designing AMPs are time-consuming and costly. This study utilized deep learning techniques, including sequence generative adversarial nets, bidirectional encoder representations from transformers, and multilayer perceptron, to design and identify AMPs. Six candidate AMPs were then screened and one of them, A-222, showed inhibition against both gram-positive and gram-negative bacteria. Structural analysis and subsequent structure-activity relationship studies led to the design of peptide analogs with increased activity against specific bacteria. Overall, deep learning holds great promise in accelerating the discovery of novel AMPs and could have significant implications in developing new antimicrobial treatments.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Chemistry, Medicinal
Christian R. O. Bartling, Flora Alexopoulou, Sarah Kuschert, Yanni K. -Y. Chin, Xinying Jia, Vita Sereikaite, Dennis Ozcelik, Thomas M. Jensen, Palash Jain, Mads M. Nygaard, Kasper Harpsoe, David E. Gloriam, Mehdi Mobli, Kristian Stromgaard
Summary: Peptides targeting disease-relevant protein-protein interactions have limitations in terms of metabolic stability and membrane permeability. Peptide cyclization, particularly hydrocarbon stapling, offers a valuable approach to develop metabolically stable and cell-permeable cyclic leads with improved affinity and stability. In this study, a comprehensive examination of cyclization strategies led to the identification of cyclic APP dodecamer peptides that target the phosphotyrosine binding domain of Mint2 with significantly improved properties.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemical Research Methods
Andrew A. Walker, Lynda E. Perkins, Andrea Battisti, Myron P. Zalucki, Glenn F. King
Summary: Ochrogaster lunifer is an Australian caterpillar that has detachable urticating setae with defensive function. These setae can cause inflammation on human skin and equine foetal loss syndrome in gravid horses if accidentally ingested. Transcriptomics and proteomics analysis identified 37 putative toxins, including multiple homologues of honeybee venom peptide secapin and proteins with similarity to odorant binding proteins, arylphorins, and the insect immune modulator Diedel. This study reveals candidate molecules that may contribute to the adverse effects of processionary caterpillar setae on human and animal health.
Article
Chemistry, Multidisciplinary
Xinying Jia, Yanni K. -Y. Chin, Alan H. H. Zhang, Theo Crawford, Yifei Zhu, Nicholas L. L. Fletcher, Zihan Zhou, Brett R. R. Hamilton, Martin Stroet, Kristofer J. J. Thurecht, Mehdi Mobli
Summary: The authors report the engineering of self-cyclizing 'autocyclase' proteins to generate macrocyclic peptides and proteins with favorable reaction kinetics for suppressing polymerization. Macrocyclisation of proteins and peptides results in a remarkable increase in structural stability, making cyclic peptides and proteins of great interest in drug discovery. The engineering of a self-cyclising autocyclase protein provides a simple, alternative way to access a vast diversity of macrocyclic biomolecules.
COMMUNICATIONS CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Aline D. de Araujo, Junxian Lim, Kai-Chen Wu, Huy N. Hoang, Huy T. Nguyen, David P. Fairlie
Summary: This study systematically compares the effects of different helix-inducing cyclization constraints on macrocyclic peptides. Rigidifying the macrocycle leads to higher alpha helicity and target affinity. Cell uptake is predominantly influenced by the hydrophobicity and aromaticity of the macrocycle.
RSC CHEMICAL BIOLOGY
(2022)
