Cyclotides are plant-derived cyclic peptides that have a head-to-tail cyclic backbone and three conserved disulphide bonds that form a cyclic cystine knot motif. They occur in plants from the Violaceae, Rubiaceae, Cucurbitaceae, Fabaceae, and Solanaceae families, typically with 10-100 cyclotides in a given plant species, in a wide range of tissues, including flowers, leaves, stems, and roots. Some cyclotides are expressed in large amounts (up to 1g kg(-1) wet plant weight) and their natural function appears to be to protect plants from pests or pathogens. This article provides a brief overview of their discovery, distribution in plants, and applications. In particular, their exceptional stability has led to their use as peptide-based scaffolds in drug design applications. They also have potential as natural 'ecofriendly' insecticides, and as protein engineering frameworks.
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http://dx.doi.org/10.1093/jxb/erw210 | DOI Listing |
J Am Chem Soc
January 2025
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States.
Spore germination in is initiated by a cascade of activities of several proteins that culminates in the activation of SleC, a cell-wall-processing enzyme. We report herein the details of the enzymatic activities of SleC by the use of synthetic peptidoglycan fragments and of spore sacculi. The reactions include the formation of 1,6-anhydromuramate─a hallmark of lytic transglycosylase activity─as well as a muramate hydrolytic product, both of which proceed through the same transient oxocarbenium species.
View Article and Find Full Text PDFScience
January 2025
Department of Genome Sciences, University of Washington, Seattle, WA, USA.
Studying the functional consequences of structural variants (SVs) in mammalian genomes is challenging because (i) SVs arise much less commonly than single-nucleotide variants or small indels and (ii) methods to generate, map, and characterize SVs in model systems are underdeveloped. To address these challenges, we developed Genome-Shuffle-seq, a method that enables the multiplex generation and mapping of thousands of SVs (deletions, inversions, translocations, and extrachromosomal circles) throughout mammalian genomes. We also demonstrate the co-capture of SV identity with single-cell transcriptomes, facilitating the measurement of SV impact on gene expression.
View Article and Find Full Text PDFMol Divers
January 2025
Integrated Drug Discovery Centre, Department of Pharmaceutical Chemistry, Acharya & BM Reddy College of Pharmacy, Bengaluru, 560107, Karnataka, India.
Discoidin domain receptors (DDR) are categorized under tyrosine kinase receptors (RTKs) and play a crucial role in various etiological conditions such as cancer, fibrosis, atherosclerosis, osteoarthritis, and inflammatory diseases. The structural domain rearrangement of DDR1 and DDR2 involved six domains of interest namely N-terminal DS, DS-like, intracellular juxtamembrane, transmembrane juxtamembrane, extracellular juxtamembrane intracellular kinase domain, and the tail portion contains small C-tail linkage. DDR has not been explored to a wide extent to be declared as a prime target for any particular pathological condition.
View Article and Find Full Text PDFAdv Biotechnol (Singap)
January 2024
Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200030, China.
SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) Variants of Concern (VOCs), such as the Omicron sub-variants, present significant challenges in pandemic control due to their capacity to escape antibodies and breach vaccine protections. Discovering antibodies that can tolerate mutations in VOCs and understanding their underlying mechanisms is crucial for developing therapeutics for COVID-19 patients, particularly those for whom other therapies may be unsuitable. Here, we report the neutralization of the Omicron variant by FD20, a broadly active human monoclonal antibody.
View Article and Find Full Text PDFAnal Chem
January 2025
Shanghai University of Sport, 399 Changhai Road, Shanghai 200438, China.
Oxymetholone and methasterone are anabolic androgenic steroids prohibited by the World Anti-Doping Agency (WADA) for both in-competition and out-of-competition use. Detecting metabolites of exogenous steroids is crucial for establishing doping violations, making the study of these metabolites essential in antidoping efforts. This study investigated the urinary metabolic profiles of oxymetholone and methasterone using gas chromatography-orbitrap high-resolution mass spectrometry (GC-Orbitrap-HRMS) in nanogram level by utilizing a novel multiplex nontargeted framework protocol.
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