Article
Chemistry, Physical
Kai Wu, Wuxuepeng Sun, Dechang Li, Jiajie Diao, Peng Xiu
Summary: This study investigates the effect of steric hindrance on amyloid formation using Monte Carlo simulations. The results show that steric hindrance inhibits oligomerization and can either facilitate or suppress the conformational conversion of proteins. Moreover, steric hindrance has an overall inhibitory effect on amyloid nucleation. These findings enhance our understanding of how nature regulates protein aggregation and amyloid formation through steric hindrance.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Biochemistry & Molecular Biology
Romualdo Troisi, Valeria Napolitano, Emanuele Rossitto, Waleed Osman, Masanobu Nagano, Koji Wakui, Grzegorz M. Popowicz, Keitaro Yoshimoto, Filomena Sica
Summary: This study characterizes the interaction between a highly dynamic G-rich oligonucleotide, M08s-1, and its target protein, human α-thrombin. The study reveals that the anticoagulant activity of M08s-1 is mainly due to its adoption of a kinked structural organization formed by a G-quadruplex domain and a long duplex module. This unique structural feature hinders the approach of a protein substrate to the active site region, leading to an increase in the anticoagulant activity.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Engineering, Chemical
Xuepeng Deng, Yang Han, Li-Chiang Lin, W. S. Winston Ho
Summary: A new measurement method for the steric hindrance effect of amine molecules, N exposure, is proposed. This method is independent of group-specific parameters and takes into account the spatial arrangements of pendant groups. It can effectively screen for sterically hindered amines with improved carbon dioxide loading capacities.
SEPARATION AND PURIFICATION TECHNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Daniel M. M. Sapozhnikov, Moshe Szyf
Summary: As genome engineering advances towards wider clinical use, a newer technology called epigenome engineering offers a safer alternative for specific epigenetic editing, without the risk of introducing epigenetic enzymes. This review highlights the limitations of epigenetic editing technology, such as the associated risks, and introduces a strategy of modifying epigenetic marks using physical occlusion instead of epigenetic enzymes.
Article
Chemistry, Multidisciplinary
Zhibin Chen, Chengzhi Hu, Chenghai Lu, Jingqiu Sun, Yanyan Zhang, Fuyi Wang, Jiuhui Qu
Summary: The hydration number distributions of alkali metal ions were characterized using ZIF-8-based membranes and the in situ liquid time-of-flight secondary ion mass spectrometry technique. It was found that ion dehydration was induced through neutral confined ZIF-8 windows, which increased the intrapore velocity for monovalent cations. The study also revealed the crucial role of dehydration energy barriers and size-based entropy barriers in ion selectivity of trans-subnanochannel transport.
Article
Biochemistry & Molecular Biology
Barbara Ben Yamin, Sana Ahmed-Seghir, Junya Tomida, Emmanuelle Despras, Caroline Pouvelle, Andrey Yurchenko, Jordane Goulas, Raphael Corre, Quentin Delacour, Nathalie Droin, Philippe Dessen, Didier Goidin, Sabine S. Lange, Sarita Bhetawal, Maria Teresa Mitjavila-Garcia, Giuseppe Baldacci, Sergey Nikolaev, Jean Charles Cadoret, Richard D. Wood, Patricia L. Kannouche
Summary: The study highlights the crucial role of DNA polymerase zeta in bypassing DNA damage and cell proliferation, as well as the significance of REV3L's interactions with heterochromatin components in maintaining chromosome stability.
Article
Chemistry, Physical
Manuel Quesada-Perez, Jose Alberto Maroto-Centeno, Maria Del Mar Ramos-Tejada, Alberto Martin-Molina
Summary: In this study, the long-time diffusion of a solute in a chemically crosslinked and flexible hydrogel was calculated using a bead-spring model of a polymeric network to assess the effect of steric obstruction. The relative diffusivities obtained for various systems can be described by an exponential decay, depending on a parameter different from that used for rigid gels. The mathematical expression derived in this work can approximately predict diffusivity in flexible gels if steric hindrance governs diffusion.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)
Article
Biochemical Research Methods
Sung Hee Ko, Pyeong Jun Park, Jongyoon Han
Summary: In this paper, a rigorous theoretical and experimental study on macromolecule sieving in a slanted nanofilter array was presented. The relationship between sieving conditions and efficiency as well as the hindrance effects on sieving were detailed. This study provides insights into designing a slanted nanofilter array for specific applications and understanding sieving principles in the nanofilter array.
Review
Chemistry, Multidisciplinary
Yanfeng Miao, Yuetian Chen, Haoran Chen, Xingtao Wang, Yixin Zhao
Summary: Utilizing steric hindrance is a promising strategy to manipulate and stabilize metal halide perovskites, which also influences the fundamental kinetics of perovskite crystallization and film formation processes. The important role of steric hindrance for stabilizing and passivating perovskites has been demonstrated in recent studies.
Article
Biochemistry & Molecular Biology
Gilles Crevel, Stephen Kearsey, Sue Cotterill
Summary: Errors made by DNA polymerases contribute to natural variation and genome instability. Cancer-associated polymerase variants with mutations in the exonuclease domain highlight the importance of polymerase misincorporation in disease. An assay was developed to compare misincorporation rates of different polymerase variants, showing differences between them and identifying a preference for C-to-T transitions.
Article
Biochemistry & Molecular Biology
Chen-Yu Lo, Yang Gao
Summary: Research suggests that T7 polymerase plays a dominant role in helicase-polymerase coupling and replisome progression. The helicase and polymerase sandwich the parental DNA, but only the polymerase carries the DNA with a positively charged cleft and stacks at the fork opening using a beta-hairpin loop.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Engineering, Chemical
Dafu Cao, Fei Yang, Weibing Sheng, Yufeng Zhou, Xixing Zhou, Yaguang Lu, Fengmin Nie, Nanwen Li, Li Pan, Yuesheng Li
Summary: By introducing hydrophobic arylene substituents, researchers successfully reduced the excessive water uptake and swelling ratio of quaternized polynorbornene anion exchange membrane while maintaining its excellent anion conductivity. The PBH-x-QA series of polymers with appropriate IEC values exhibited good thermal stability and tensile properties.
JOURNAL OF MEMBRANE SCIENCE
(2022)
Article
Microbiology
Peter B. Bohall, Stephen D. Bell
Summary: The loss of putative repair polymerases PolB2 and/or PolB3 in the crenarchaeon Sulfolobus islandicus leads to a modest growth advantage and insensitivity to hydrogen peroxide. However, cells lacking PolB3 show enhanced sensitivity to the DNA damaging agent 4-NQO, suggesting that these non-essential DNA polymerases may influence DNA repair pathway choice in hyperthermophilic aerobes.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
Xiaoxiao Lu, Chenyao Shang, Lulu Li, Rongjun Chen, Bina Fu, Xin Xu, Dong H. Zhang
Summary: The authors of this study highlight the significance of base-induced elimination and bimolecular nucleophilic substitution reactions in physical organic chemistry. They provide evidence that the competing factor of elimination, rather than steric hindrance, determines the low reactivity of nucleophilic substitution reactions. This finding provides new insights into the dynamical origin of intrinsic reactivity in gas-phase organic chemistry.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Grant A. L. Bare, Gerald F. Joyce
Summary: Informational macromolecules in biology, such as nucleic acids and proteins, typically have specific chirality. However, recent research has shown that it is possible to amplify RNA molecules of opposite chirality using a specific enzyme, providing a potential for the evolution of cross-chiral RNA polymerases.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Fa-Jie Chen, Mengmeng Zheng, Vincent Nobile, Jianmin Gao
Summary: The novel method demonstrates fast reaction kinetics and excellent selectivity for cysteine residues, allowing modification of peptides and proteins under physiologic conditions.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Rahi M. Reja, Wenjian Wang, Yuhan Lyu, Fredrik Haeffner, Jianmin Gao
Summary: We report a new reversible lysine conjugation method that shows a unique diazaborine product and slower dissociation kinetics compared to the known iminoboronate chemistry. By incorporating the diazaborine-forming warhead RMR1 into a peptide ligand, we have developed potent and long-acting reversible covalent inhibitors of staphylococcal sortase. The efficacy of sortase inhibition is demonstrated through biochemical and cell-based assays. A comparative study between RMR1 and an iminoboronate-forming warhead emphasizes the importance and potential of modulating bond dissociation kinetics in achieving long-acting reversible covalent inhibitors.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Fa-Jie Chen, Jianmin Gao
Summary: Cysteine bioconjugation plays a crucial role in biological research and has been widely utilized for protein modification, antibody-drug conjugate construction, and cell imaging studies. Recent advancements in fast cysteine bioconjugation have been summarized in this concept, along with discussions on the mechanism and chemical principles that contribute to the high efficiency of newly developed cysteine reactive reagents.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Lu Xiao, Linglan Fang, Sayantan Chatterjee, Eric T. Kool
Summary: RNA 2'-OH acylation is widely used for structure mapping and conjugation, and depends on selective reactions with unpaired nucleotides. We prepared a range of structurally diverse acylimidazole reagents and used deep sequencing to study their reactivity and selectivity in a variety of RNA structures. Our results demonstrate that the reagent scaffold significantly affects reactivity profiles and highlight new acylating agents with altered selectivity, including compounds that show elevated selectivity within loops and reduced off-target reactivity in loop closing base pairs. We also discovered a simple reagent that is cell permeable and can map RNA structure in the presence of protein contacts, and describe reagents with elevated selectivity within small loops for site-selective labeling.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Fa-Jie Chen, Nicole Pinnette, Fan Yang, Jianmin Gao
Summary: In this study, we report a cysteine-directed proximity-driven strategy for constructing bicyclic peptides from simple natural peptide precursors. This linear to bicycle transformation involves rapid cysteine labeling and subsequent amine-selective cyclization. The bicyclization process occurs rapidly under physiological conditions, resulting in bicyclic peptides with Cys-Lys-Cys, Lys-Cys-Lys, or N-terminus-Cys-Cys stapling patterns. We demonstrate the utility and power of this strategy by constructing bicyclic peptides fused to proteins and the M13 phage, enabling the phage display of novel bicyclic peptide libraries.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Rahi M. Reja, Brittney Chau, Jianmin Gao
Summary: Multicyclic peptides are potential candidates for peptide-based drug discovery. A new cross-linker, DCA-RMR1, has been developed for efficient bicyclization of native peptides via N-terminus Cys-Cys cross-linking. The resulting diazaborine linkage is stable at neutral pH and can reversibly change under mild acidification, enabling the production of pH-responsive peptides.
Article
Chemistry, Multidisciplinary
Sayantan Chatterjee, Ryuta Shioi, Eric T. Kool
Summary: The nucleophilic reactivity of RNA 2'-OH groups has been applied in various RNA-related processes. In this study, it is discovered that activated small-molecule sulfonyl species can retain their reactivity in water. Reactions with ribose 2'-OH show high yields, especially for aryl sulfonyltriazole species. Additionally, an azide-substituted sulfonyltriazole reagent is developed for labeling RNA via click chemistry.
ACS CENTRAL SCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Yong Woong Jun, Melis Kant, Erdem Coskun, Takamitsu A. A. Kato, Pawel Jaruga, Elizabeth Palafox, Miral Dizdaroglu, Eric T. T. Kool
Summary: High-temperature cooking damages DNA in food, which can then enter the cellular DNA and lead to genetic risks.
ACS CENTRAL SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Mengmeng Zheng, Jianmin Gao
Summary: Peptides, as a therapeutic modality between small molecules and antibodies, are gaining attention for their ability to combine the benefits of both. This study presents a novel phage library that incorporates two distinct designer groups, allowing the screening of peptides with diverse and non-natural functional motifs. The modification of phage-displayed peptides through sequential chemical reactions resulted in the discovery of potent peptide inhibitors against TEV protease.
ACS CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Linglan Fang, Lu Xiao, Yong Woong Jun, Yoshiyuki Onishi, Eric T. T. Kool
Summary: The presence of a hydroxyl group at the 2'-position in ribose makes RNA susceptible to hydrolysis. In this study, reversible 2'-OH acylation was presented as a general strategy to preserve RNA stability. High-yield polyacylation of 2'-hydroxyls effectively protected RNAs from degradation, and subsequent treatment with nucleophilic reagents removed acylation adducts and recovered a wide range of RNA functions.
Article
Chemistry, Multidisciplinary
Ryuta Shioi, Lu Xiao, Sayantan Chatterjee, Eric T. Kool
Summary: The reactivity of RNA 2'-OH groups with acylating agents has been studied for high-yield conjugation of RNA strands. This study focuses on the stereoselectivity of chiral acylimidazoles in RNA reactions. The results reveal that positional selectivity and reactivity vary greatly with local RNA macro-chirality, and the chirality of the reagents has a significant impact on their reactivity. This study demonstrates new chemical strategies for selective RNA modification and probing.
Article
Biochemical Research Methods
Reema Baskar, Amy F. Chen, Patricia Favaro, Warren Reynolds, Fabian Mueller, Luciene Borges, Sizun Jiang, Hyun Shin Park, Eric T. Kool, William J. Greenleaf, Sean C. Bendall
Summary: Master transcription factors regulate cell states by driving gene-expression programs, and their abundance affects cell fate at the chromatin level. InTAC-seq method allows the study of the relationship between protein abundance and gene regulation in cells.
CELL REPORTS METHODS
(2022)
Article
Biochemistry & Molecular Biology
Lu Xiao, Linglan Fang, Eric T. Kool
Summary: The reactivity of RNA 2'-OH acylation has been extensively studied in this research. The results show that there is a wide range of reactivity among single-stranded RNA sequences, with nearest neighbors playing a significant role. Interestingly, certain small loops exhibit much higher reactivity compared to single-stranded RNAs, which is attributed to conformational constraints.
CELL CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Sergio M. Marques, Michaela Slanska, Klaudia Chmelova, Radka Chaloupkova, Martin Marek, Spencer Clark, Jiri Damborsky, Eric T. Kool, David Bodnar, Zbynek Prokop
Summary: HaloTag labeling technology has revolutionized protein chemistry and cellular biology, and a systematic analysis of different ligands has led to the discovery of an optimal protein tag selection protocol, eliminating the need for expensive and complex protein engineering.
Article
Chemistry, Multidisciplinary
Mengmeng Zheng, Fredrik Haeffner, Jianmin Gao
Summary: Phage display is an invention for evaluating peptide libraries, and it has mainly been used for natural peptides. Recently, there has been increasing interest in modifying phage libraries to create nonnatural cyclic peptides. This study presents a novel strategy for creating backbone-side chain cyclized peptide libraries on phage, and potent inhibitors for two model proteins were discovered using this strategy.