Current Articles about Chemical Biology published in scientific online journals.
The author- or copyrights of the listed
research articles below
are held by the respective authors or site operators, who are also responsible
for the content of the presentations.
To search
this web page for specific words type "Ctrl" + "F" on your keyboard
(Command + "F" on a Mac). Then: type the word you are searching for in
the window that pops up!
To list your
article here plaease contact us by eMail.
On this page considered biochemistry journals:
ACS Chemical Biology - published by
The American Chemical Society -
... is to provide an international forum for the rapid communication of research that broadly embraces the interface between chemistry and biology.
Chemical Biology - published by
The Royal Society of Chemistry -
... is an exciting news service which draws together coverage from all RSC publications, providing an overview of the latest developments in chemical biology.
Nature Chemical Biology - published by
Nature Publishing Group -
... is a monthly research journal of science that that publishes original research in three formats (Brief Communications, Letters and Articles), as well as News and Views, reviews, perspectives, commentaries, book reviews, meeting reports, research highlights and editorials covering all research at the interface of chemistry and biology.
ChemBioChem - published by
Wiley Interscience -
... is a source for important primary and secondary information across the whole field of chemical biology, bio(in)organic chemistry, and biochemistry.
BMC Chemical Biology - published by
BioMed Central -
... is an open access journal publishing original peer-reviewed research articles in the application of chemistry to the investigation of biology and drug design.
Current research articles of the mentioned
journals:
Stephan C. Schürer, Steven J. Brown, Pedro J. Gonzalez-Cabrera, Marie-Therese Schaeffer, Jacqueline Chapman, Euijung Jo, Peter Chase, Tim Spicer, Peter Hodder, and Hugh Rosen Web Release Date: Tue, 1 Jul 2008 00:00:00 EDT (Articles) DOI: 10.1021/cb800051m
Douglas S. Auld, Natasha Thorne, Dac-Trung Nguyen, and James Inglese Web Release Date: Tue, 1 Jul 2008 00:00:00 EDT (Perspective) DOI: 10.1021/cb8000793
Mathieu Mevel, Cecile Neveu, Cristine Goncalves, Jean-Jacques Yaouanc, Chantal Pichon, Paul-Alain Jaffres, Patrick Midoux
(From Chem. Commun.)
Mathieu Mevel, Chem. Commun., 2008, DOI: 10.1039/b805226c
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Catherine T. Lo, Daniel J. Throckmorton, Anup K. Singh, Amy E. Herr
(From Lab Chip)
Catherine T. Lo, Lab Chip, 2008, DOI: 10.1039/b804485f
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Stefania Sarno, Lorenzo A. Pinna
(From Mol. BioSyst.)
Stefania Sarno, Mol. BioSyst., 2008, DOI: 10.1039/b805534c
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Lois Alexander, Kevin Dhaliwal, John Simpson, Mark Bradley
(From Chem. Commun.)
Lois Alexander, Chem. Commun., 2008, DOI: 10.1039/b805323e
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Shuho Tanimoto, Shuichi Matsumura, Kazunobu Toshima
(From Chem. Commun.)
Shuho Tanimoto, Chem. Commun., 2008, DOI: 10.1039/b806961a
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Visith Thongboonkerd
(From Mol. BioSyst.)
Visith Thongboonkerd, Mol. BioSyst., 2008, DOI: 10.1039/b802534g
To cite this article before page numbers are assigned, use the DOI form of citation above.
Ontology Terms:
stem cell; podocyte; vitamin D binding; excretion; retinol binding; angiotensin-converting enzyme inhibitor activity; polypeptide
The content of this RSS Feed (c) The Royal Society of Chemistry
Young Jin Lee
(From Mol. BioSyst.)
Young Jin Lee, Mol. BioSyst., 2008, DOI: 10.1039/b801810c
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Valerie J. Paul, Raphael Ritson-Williams
(From Nat. Prod. Rep.)
Valerie J. Paul, Nat. Prod. Rep., 2008, DOI: 10.1039/b702742g
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Aaron M. Lowe, Byram H. Ozer, Gregory J. Wiepz, Paul J. Bertics, Nicholas L. Abbott
(From Lab Chip)
Aaron M. Lowe, Lab Chip, 2008, DOI: 10.1039/b801935e
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Jonathan F. Fretwell, Shams M. K. Ismail, Jeffrey M. Cummings, Thomas L. Selby
(From Mol. BioSyst.)
Jonathan F. Fretwell, Mol. BioSyst., 2008, DOI: 10.1039/b709290c
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Isaac S. Carrico
(From Chem. Soc. Rev.)
Isaac S. Carrico, Chem. Soc. Rev., 2008, DOI: 10.1039/b703364h
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Jose J. Reina, Irene Diaz, Pedro M. Nieto, Nuria E. Campillo, Juan A. Paez, Georges Tabarani, Franck Fieschi, Javier Rojo
(From Org. Biomol. Chem.)
Jose J. Reina, Org. Biomol. Chem., 2008, DOI: 10.1039/b802144a
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Clare P. Fenna, Victoria J. Wilkinson, John R. P. Arnold, Richard Cosstick, Julie Fisher
(From Chem. Commun.)
Clare P. Fenna, Chem. Commun., 2008, DOI: 10.1039/b804833a
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Jyotirmayee Dash, Pravin S. Shirude, Shankar Balasubramanian
(From Chem. Commun.)
Jyotirmayee Dash, Chem. Commun., 2008, DOI: 10.1039/b806042h
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Alois Schweighofer, Irute Meskiene
(From Mol. BioSyst.)
Alois Schweighofer, Mol. BioSyst., 2008, DOI: 10.1039/b718578m
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Bin Wu, Shikai Yan, Zhongying Lin, Qi Wang, Yun Yang, Genjin Yang, Ziyin Shen, Weidong Zhang
(From Mol. BioSyst.)
Bin Wu, Mol. BioSyst., 2008, DOI: 10.1039/b800923f
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
David J. Evans
(From J. Mater. Chem.)
David J. Evans, J. Mater. Chem., 2008, DOI: 10.1039/b804305a
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Julia Schmitz, Kay-Eberhard Gottschalk
(From Soft Matter)
Julia Schmitz, Soft Matter, 2008, DOI: 10.1039/b716805p
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Damian P. Buck, Caitriona B. Spillane, J. Grant Collins, F. Richard Keene
(From Mol. BioSyst.)
Damian P. Buck, Mol. BioSyst., 2008, DOI: 10.1039/b803216e
To cite this article before page numbers are assigned, use the DOI form of citation above.
Ontology Terms:
ribonuclease activity; RNA splicing; RNA_internal_loop; base_pair; RNA_sequence_secondary_structure; stem_loop; transcript; oligo; base
The content of this RSS Feed (c) The Royal Society of Chemistry
Heitor A. De Abreu, Izandina Aparecida dos S. Lago, Gilmar P. Souza, Dorila Pilo-Veloso, Helio A. Duarte, Antonio Flavio de C. Alcantara
(From Org. Biomol. Chem.)
Heitor A. De Abreu, Org. Biomol. Chem., 2008, DOI: 10.1039/b804385j
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Marialice da Fonseca Ferreira da Silva, Helene S. Barbosa, Uwe Gro[German sz ligature}, Carsten G. K. Luder
(From Mol. BioSyst.)
Marialice da Fonseca Ferreira da Silva, Mol. BioSyst., 2008, DOI: 10.1039/b800520f
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Grant D. Geske, Jennifer C. O'Neill, Helen E. Blackwell
(From Chem. Soc. Rev.)
Grant D. Geske, Chem. Soc. Rev., 2008, DOI: 10.1039/b703021p
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Christophe Morin, Tatiana Besset, Jean-Claude Moutet, Martine Fayolle, Margit Bruckner, Daniele Limosin, Katja Becker, Elisabeth Davioud-Charvet
(From Org. Biomol. Chem.)
Christophe Morin, Org. Biomol. Chem., 2008, DOI: 10.1039/b802649c
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Christopher A. Hurley, John B. Wong, Jimmy Ho, Michele Writer, Scott A. Irvine, M. Jayne Lawrence, Stephen L. Hart, Alethea B. Tabor, Helen C. Hailes
(From Org. Biomol. Chem.)
Christopher A. Hurley, Org. Biomol. Chem., 2008, DOI: 10.1039/b719702k
To cite this article before page numbers are assigned, use the DOI form of citation above.
Ontology Terms:
endosome; plasma membrane; cell surface; endosomal part; plasmid
The content of this RSS Feed (c) The Royal Society of Chemistry
David Spring
(From Chem. Soc. Rev.)
David Spring, Chem. Soc. Rev., 2008, DOI: 10.1039/b808132h
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Tim Horlacher, Peter H. Seeberger
(From Chem. Soc. Rev.)
Tim Horlacher, Chem. Soc. Rev., 2008, DOI: 10.1039/b708016f
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Claudia Temperini, Alessandro Cecchi, Andrea Scozzafava, Claudiu T. Supuran
(From Org. Biomol. Chem.)
Claudia Temperini, Org. Biomol. Chem., 2008, DOI: 10.1039/b800767e
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Robert J. Capon, Chongsheng Peng, Cedric Dooms
(From Org. Biomol. Chem.)
Robert J. Capon, Org. Biomol. Chem., 2008, DOI: 10.1039/b803455a
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Marc P. Stemmler
(From Mol. BioSyst.)
Marc P. Stemmler, Mol. BioSyst., 2008, DOI: 10.1039/b719215k
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Nicholas P Mulholland, Gerald Pattenden, Iain A. S. Walters
(From Org. Biomol. Chem.)
Nicholas P Mulholland, Org. Biomol. Chem., 2008, DOI: 10.1039/b803818j
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Jody Vykoukal, Daynene M. Vykoukal, Susanne Freyberg, Eckhard U. Alt, Peter R. C. Gascoyne
(From Lab Chip)
Jody Vykoukal, Lab Chip, 2008, DOI: 10.1039/b717043b
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Rasheduzzaman Chowdhury, Adam Hardy, Christopher J. Schofield
(From Chem. Soc. Rev.)
Rasheduzzaman Chowdhury, Chem. Soc. Rev., 2008, DOI: 10.1039/b701676j
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Gian Gaetano Tartaglia, Michele Vendruscolo
(From Chem. Soc. Rev.)
Gian Gaetano Tartaglia, Chem. Soc. Rev., 2008, DOI: 10.1039/b706784b
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Diana Olschewski, Christian F. W. Becker
(From Mol. BioSyst.)
Diana Olschewski, Mol. BioSyst., 2008, DOI: 10.1039/b803248c
To cite this article before page numbers are assigned, use the DOI form of citation above.
Ontology Terms:
cardiac muscle cell; GTPase activity; G-protein coupled receptor activity; ion channel activity; potassium channel activity; cytoplasm; Golgi apparatus; plasma membrane; protein amino acid lipidation; proteolysis; peptidase activity; integral to membrane; attachment of GPI anchor to protein; virion; organelle; host cell; cellular localization; intein; post-translational protein modification; ligand-gated channel activity; calcium ion homeostasis; polypeptide_secondary_structure
The content of this RSS Feed (c) The Royal Society of Chemistry
Xinyu Liu, Reiko Wada, Siwarutt Boonyarattanakalin, Bastien Castagner, Peter H. Seeberger
(From Chem. Commun.)
Xinyu Liu, Chem. Commun., 2008, DOI: 10.1039/b804069a
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Stephen J. Roe, Robert A. Stockman
(From Chem. Commun.)
Stephen J. Roe, Chem. Commun., 2008, DOI: 10.1039/b804304c
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Jose L. de Paz, Peter H. Seeberger
(From Mol. BioSyst.)
Jose L. de Paz, Mol. BioSyst., 2008, DOI: 10.1039/b802217h
To cite this article before page numbers are assigned, use the DOI form of citation above.
Ontology Terms:
fibroblast; mast cell; endothelial cell; eukaryotic cell; neuron; lymphocyte; leukocyte; angiogenesis; protein binding; extracellular region; Golgi apparatus; chemotaxis; inflammatory response; nervous system development; blood coagulation; growth factor activity; cell surface; cell growth; cell migration; lymphocyte chemotaxis; leukocyte migration; sulfation; oligosaccharides; heparan sulfates; glycosaminoglycans; proteoglycans; carbohydrates; heparins; polysaccharides; chondroitin sulfates; proteins
The content of this RSS Feed (c) The Royal Society of Chemistry
Christina Jonsson, Magnus Aronsson, Gerd Rundstrom, Christer Pettersson, Ib Mendel-Hartvig, Jimmy Bakker, Erik Martinsson, Bo Liedberg, Brian MacCraith, Ove Ohman, Jonas Melin
(From Lab Chip)
Christina Jonsson, Lab Chip, 2008, DOI: 10.1039/b800297e
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Mithun Roy, Tuhin Bhowmick, Suryanarayanarao Ramakumar, Munirathinam Nethaji, Akhil R. Chakravarty
(From Dalton Trans.)
Mithun Roy, Dalton Trans., 2008, DOI: 10.1039/b802533a
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Sarah Koster, Francesco E. Angile, Honey Duan, Jeremy J. Agresti, Anton Wintner, Christian Schmitz, Amy C. Rowat, Christoph A. Merten, Dario Pisignano, Andrew D. Griffiths, David A. Weitz
(From Lab Chip)
Sarah Koster, Lab Chip, 2008, DOI: 10.1039/b802941e
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Benjamin J. Leslie, Paul J. Hergenrother
(From Chem. Soc. Rev.)
Benjamin J. Leslie, Chem. Soc. Rev., 2008, DOI: 10.1039/b702942j
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Mrinmoy De, Vincent M. Rotello
(From Chem. Commun.)
Mrinmoy De, Chem. Commun., 2008, DOI: 10.1039/b805242e
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Elizabeth S. Sattely, Michael A. Fischbach, Christopher T. Walsh
(From Nat. Prod. Rep.)
Elizabeth S. Sattely, Nat. Prod. Rep., 2008, DOI: 10.1039/b801747f
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Priyadarshi Panda, Shamsher Ali, Edward Lo, Bong Geun Chung, T. Alan Hatton, Ali Khademhosseini, Patrick S. Doyle
(From Lab Chip)
Priyadarshi Panda, Lab Chip, 2008, DOI: 10.1039/b804234a
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Palwinder Singh, Anu Mittal, Satwinderjeet Kaur, Wolfgang Holzer, Subodh Kumar
(From Org. Biomol. Chem.)
Palwinder Singh, Org. Biomol. Chem., 2008, DOI: 10.1039/b803608j
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
Cooperative binding effects pervade biology. Only a few basic principles are at play, but in different biological contexts cooperativity appears in distinct guises to achieve different ends. Here I discuss some of the manifestations of cooperativity that are most important in biology and drug discovery as they pertain to systems at different levels of complexity and also highlight aspects of this broadly important phenomenon that remain poorly understood.
The development of single-molecule tools has significantly impacted the way we think about biochemical processes. Watching a single protein in action allows us to observe kinetic details and rare subpopulations that are hidden in ensemble-averaging techniques. I will discuss here the pros and cons of the single-molecule approach in studying ligand binding in macromolecular systems and how these techniques can be applied to characterize the behavior of large multicomponent biochemical systems.
Phosphorylation and glycosylation of the tau protein, which is implicated in neurodegenerative diseases, are intimately linked. In vivo pharmacological inhibition of tau deglycosylation may be a new way to suppress abnormal tau phosphorylation, known to be involved in the formation of neurofibrillary tangles in the brain.
Analysis of individual RNA folding reactions reveals that, as in proteins, cooperative interactions selectively drive RNA toward its biologically active, native conformation. This new work establishes a platform for future investigations of the physical principles underlying the assembly of large RNA enzymes.
Many of the phenotypes shown by bacteria at high population densities are only beneficial when they are associated with eukaryotic hosts. A new study confirms that some bacteria may couple quorum sensing to host-derived signals to refine such interactions.
Transporter proteins mediate the import of nutrients and the export of toxins across biological membranes. A new crystal structure of a bacterial ABC transporter reveals an unexpected mechanism for transporter inhibition by its transported substrate.
Authors: Scott A Yuzwa, Matthew S Macauley, Julia E Heinonen, Xiaoyang Shan, Rebecca J Dennis, Yuan He, Garrett E Whitworth, Keith A Stubbs, Ernest J McEachern, Gideon J Davies
& David J Vocadlo
Authors: Shawn Hoon, Andrew M Smith, Iain M Wallace, Sundari Suresh, Molly Miranda, Eula Fung, Michael Proctor, Kevan M Shokat, Chao Zhang, Ronald W Davis, Guri Giaever, Robert P StOnge
& Corey Nislow
The biotransformation of linoleic acid (LA) into conjugated linoleic acid (CLA) by microorganisms is a potentially useful industrial process. In most cases, however, the identities of proteins involved and the details of enzymatic activity regulation are far from clear. Here we summarize available data on the reaction mechanisms of CLA-producing enzymes characterized until now, from Butyrivibrio fibrisolvens, Lactobacillus acidophilus, Ptilota filicina, and Propionibacterium acnes. A general feature of enzymatic LA isomerization is the protein-assisted abstraction of an aliphatic hydrogen atom from position C-11, while the role of flavin as cofactor for the double bond activation in CLA-producing enzymes is also discussed with regard to the recently published three-dimensional structure of an isomerase from P. acnes. Combined data from structural studies, isotopic labeling experiments, and sequence comparison suggest that at least two different prototypical active site geometries occur among polyunsaturated fatty acid (PUFA) double bond isomerases.
HIV-1 viral assembly requires a direct interaction between a Pro-Thr-Ala-Pro ("PTAP") motif in the viral protein Gag-p6 and the cellular endosomal sorting factor Tsg101. In an effort to develop competitive inhibitors of this interaction, an SAR study was conducted based on the application of post solid-phase oxime formation involving the sequential insertion of aminooxy-containing residues within a nonamer parent peptide followed by reaction with libraries of aldehydes. Approximately 15-20-fold enhancement in binding affinity was achieved by this approach.
The second WW domain (WW2) of CA150, a human transcriptional activator, forms amyloid fibrils in vitro under physiological conditions. Based on experimental constraints from MAS NMR spectroscopy experiments, alanine scanning and electron microscopy, a structural model of CA150.WW2 amyloid fibrils was calculated earlier. Here, the assignment strategy is presented and suggested as a general approach for proteins that show intermediate line width. The 13C,13C correlation experiments were recorded on fully or partially 13C-labelled fibrils. The earlier 13C assignment (26 residues) was extended to 34 of the 40 residues by direct 13C-excitation experiments by using a deuterated sample that showed strongly improved line width. A 3D HNC-TEDOR (transferred-echo double-resonance) experiment with deuterated CA150.WW2 fibrils yielded 14 amide nitrogen and proton resonance assignments. The obtained chemical shifts were compared with the chemical shifts determined with the natively folded WW domain. TALOS (Torsion angle likelihood obtained from shift and sequence similarity) predictions confirmed that, under physiological conditions, the fibrillar form of CA150.WW2 adopts a significantly different [beta] structure than the native WW-domain fold.
Microorganisms compete for nutrients and living space in the gut of plant-feeding insect larvae, such as Spodoptera spp. Their physiological activities and their organization are generally controlled or synchronised by "autoinducers", such as N-acylhomoserinelactones (AHLs). Due to the strongly alkaline milieu in the insect gut, the lactone ring of AHLs is rapidly and spontaneously opened. Further degradation to the inactive components homoserine and the acyl moiety is then achieved by a microbial N-acylamino acid hydrolase (AAH) and related enzymatic activities in the insect gut. Initialised by the alkaline milieu, such activities might account for the complete absence of AHLs in the intestinal fluid of the studied Spodoptera spp. The AHL-recognition system of E. coli RV308pSB40, but not that of Agrobacterium tumefaciens NT1/pZLR4 and Chromobacterium violaceum CV026, was found to be inhibited by the structurally related N-acylglutamines, which are abundantly present in the gut of many lepidopteran larvae. Our observations suggest an active role of the insect in interfering with the quorum sensing of their gut microbiota by several independent strategies.
The cyclotides are a family of backbone-cyclised cystine-knot-containing peptides from plants that possess anthelmintic activity against Haemonchus contortus and Trichostrongylus colubriformis, two important gastrointestinal nematode parasites of sheep. In the current study, we investigated the in vitro effects of newly discovered natural cyclotides on the viability of larval and adult life stages of these pests. The natural variants cycloviolacin O2, cycloviolacin O3, cycloviolacin O8, cycloviolacin O13, cycloviolacin O14, cycloviolacin O15, and cycloviolacin O16 extracted from Viola odorata showed up to 18-fold greater potency than the prototypic cyclotide kalata B1 in nematode larval development assays. Cycloviolacin O2 and cycloviolacin O14 were significantly more potent than kalata B1 in adult H. contortus motility assays. The lysine and glutamic acid residues of cycloviolacin O2, the most potent anthelmintic cyclotide, were chemically modified to investigate the role of these charged residues in modulating the biological activity. The single glutamic acid residue, which is conserved across all known cyclotides, was shown to be essential for activity, with a sixfold decrease in potency of cycloviolacin O2 following methylation. The three lysine residues present in cycloviolacin O2 were acetylated to effectively mask the positive charge, resulting in a 18-fold decrease in anthelmintic activity. The relative anthelmintic activities of the natural variants assayed against nematode larvae correlated with the number of charged residues present in their sequence.
HJ1, a 42-residue peptide that folds into a helix-loop-helix motif and dimerizes to form a four-helix bundle, successfully catalyzes the cleavage of "early stage" DNA model substrates in an aqueous solution at pH 7.0, with a rate enhancement in the hydrolysis of heptyl 4-nitrophenyl phosphate of over three orders of magnitude over that of the imidazole-catalyzed reaction, k2(HJ1)/k2(Im)=3135. The second-order rate constant, k2(HJ1) was determined to be 1.58×10-4 M-1 s-1. The catalyst successfully assembles residues that in a single elementary reaction step are capable of general-acid and general-base catalysis as well as transition state stabilization and proximity effects. The reactivity achieved with the HJ1 polypeptide, rationally designed to catalyze the hydrolysis of phosphodiesters, is based on two histidine residues flanked by four arginines and two adjacent tyrosine residues, all located on the surface of a helix-loop-helix motif. The introduction of Tyr residues close to the catalytic site improves efficiency, in the cleavage of activated aryl alkyl phosphates as well as less activated dialkyl phosphates. HJ1 is also effective in the cleavage of an RNA-mimic substrate, uridine-3[prime]-2,2,2-trichloroethyl phosphate (leaving group pKa=12.3) with a second-order rate constant of 8.23×10-4 M-1 s-1 in aqueous solution at pH 7.0, some 500 times faster than the reaction catalyzed by imidazole, k2(HJ1)/k2(Im)=496.
