scholarly journals 19 F NMR‐Based Fragment Screening for 14 Different Biologically Active RNAs and 10 DNA and Protein Counter‐Screens

ChemBioChem ◽  
2020 ◽  
Author(s):  
Oliver Binas ◽  
Vanessa Jesus ◽  
Tom Landgraf ◽  
Albrecht Eduard Völklein ◽  
Jason Martins ◽  
...  
Keyword(s):  
Biologically Active ◽  
Fragment Screening ◽  
19 F Nmr

scholarly journals Fragment-Based Screening in Tandem with Phenotypic Screening Provides Novel Antiparasitic Hits

2014 ◽  
Vol 20 (1) ◽  
pp. 131-140 ◽  
Author(s):  
Antoni R. Blaazer ◽  
Kristina M. Orrling ◽  
Anitha Shanmugham ◽  
Chimed Jansen ◽  
Louis Maes ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Chemical Space ◽  
Biologically Active ◽  
Phenotypic Screening ◽  
Antiparasitic Activity ◽  
Fragment Screening ◽  
Human Lung Cells ◽  
Causative Agents ◽  
Low Toxicity ◽  
The Relationship

Methods to discover biologically active small molecules include target-based and phenotypic screening approaches. One of the main difficulties in drug discovery is elucidating and exploiting the relationship between drug activity at the protein target and disease modification, a phenotypic endpoint. Fragment-based drug discovery is a target-based approach that typically involves the screening of a relatively small number of fragment-like (molecular weight <300) molecules that efficiently cover chemical space. Here, we report a fragment screening on TbrPDEB1, an essential cyclic nucleotide phosphodiesterase (PDE) from Trypanosoma brucei, and human PDE4D, an off-target, in a workflow in which fragment hits and a series of close analogs are subsequently screened for antiparasitic activity in a phenotypic panel. The phenotypic panel contained T. brucei, Trypanosoma cruzi, Leishmania infantum, and Plasmodium falciparum, the causative agents of human African trypanosomiasis (sleeping sickness), Chagas disease, leishmaniasis, and malaria, respectively, as well as MRC-5 human lung cells. This hybrid screening workflow has resulted in the discovery of various benzhydryl ethers with antiprotozoal activity and low toxicity, representing interesting starting points for further antiparasitic optimization.

Characterization of photosystem II with the atomic-force microscope

1992 ◽  
Vol 50 (2) ◽  
pp. 1146-1147
Author(s):  
Kathleen M. Marr ◽  
Mary K. Lyon
Keyword(s):  
Photosystem Ii ◽  
Atomic Force Microscope ◽  
Three Dimensional ◽  
Biologically Active ◽  
Atomic Force ◽  
Freeze Etching ◽  
Image Averaging ◽  
Oxygen Evolving ◽  
Averaging Techniques

Photosystem II (PSII) is different from all other reaction centers in that it splits water to evolve oxygen and hydrogen ions. This unique ability to evolve oxygen is partly due to three oxygen evolving polypeptides (OEPs) associated with the PSII complex. Freeze etching on grana derived insideout membranes revealed that the OEPs contribute to the observed tetrameric nature of the PSIl particle; when the OEPs are removed, a distinct dimer emerges. Thus, the surface of the PSII complex changes dramatically upon removal of these polypeptides. The atomic force microscope (AFM) is ideal for examining surface topography. The instrument provides a topographical view of individual PSII complexes, giving relatively high resolution three-dimensional information without image averaging techniques. In addition, the use of a fluid cell allows a biologically active sample to be maintained under fully hydrated and physiologically buffered conditions. The OEPs associated with PSII may be sequentially removed, thereby changing the surface of the complex by one polypeptide at a time.

Depletion and Reconstitution of Active E. Coli Ribosomes

1975 ◽  
Vol 33 ◽  
pp. 640-641
Author(s):  
M. Boublik ◽  
W. Hellmann ◽  
F. Jenkins
Keyword(s):  
Protein Biosynthesis ◽  
Large Subunit ◽  
High Resolution Electron Microscopy ◽  
Small Subunit ◽  
Structure And Function ◽  
Biologically Active ◽  
Biological Macromolecules ◽  
E Coli ◽  
Resolution Electron ◽  
And Function

Correlations between structure and function of biological macromolecules have been studied intensively for many years, mostly by indirect methods. High resolution electron microscopy is a unique tool which can provide such information directly by comparing the conformation of biopolymers in their biologically active and inactive state. We have correlated the structure and function of ribosomes, ribonucleoprotein particles which are the site of protein biosynthesis. 70S E. coli ribosomes, used in this experiment, are composed of two subunits - large (50S) and small (30S). The large subunit consists of 34 proteins and two different ribonucleic acid molecules. The small subunit contains 21 proteins and one RNA molecule. All proteins (with the exception of L7 and L12) are present in one copy per ribosome.This study deals with the changes in the fine structure of E. coli ribosomes depleted of proteins L7 and L12. These proteins are unique in many aspects.

Fractionation of the Biologically Active Large Molecular Components of Human Gastric Content

1959 ◽  
Vol 37 (4) ◽  
pp. 439-444 ◽  
Author(s):  
Ranwel Caputto ◽  
William O. Smith ◽  
Jordan Tang ◽  
Raul E. Trucco ◽  
Walter Joel ◽  
...  
Keyword(s):  
Gastric Content ◽  
Biologically Active ◽  
Molecular Components

Bioavailability of naringenin chalcone in humans after ingestion of cherry tomatoes

2020 ◽  
Vol 90 (5-6) ◽  
pp. 411-416 ◽  
Author(s):  
Carina Kolot ◽  
Ana Rodriguez-Mateos ◽  
Rodrigo Feliciano ◽  
Katharina Bottermann ◽  
Wilhelm Stahl
Keyword(s):  
Plasma Levels ◽  
Average Concentration ◽  
Biologically Active ◽  
Thiol Groups ◽  
Structural Element ◽  
Active Molecule ◽  
Reactive Center ◽  
Average Maximum ◽  
Alpha Beta ◽  
Cherry Tomatoes

Abstract. Chalcones are a type of flavonoids characterized by an α-β unsaturated structural element which may react with thiol groups to activate pathways such as the Nrf2-Keap-1 system. Naringenin chalcone is abundant in the diet but little is known about its bioavailability. In this work, the bioavailability of naringenin chalcone from tomatoes was investigated in a group of healthy men (n=10). After ingestion of 600 grams of tomatoes providing a single dose of 17.3 mg naringenin chalcone, 0.2 mg of naringenin, and 195 mg naringin plasma levels of free and conjugated naringenin and naringenin chalcone (glucuronide and sulfate) were analyzed by UHPLC-QTOF-MS at 0.5, 1, 3, and 6 h post-consumption. Plasma levels of conjugated naringenin increased to about 12 nmol/L with a maximum at about 3 h. Concentrations of free naringenin hardly elevated above baseline. Plasma levels of free and conjugated naringenin chalcone significantly increased. A maximum of the conjugated chalcone was reached at about 3 h after ingestion with an average concentration of about 0.5 nmol/L. No free chalcone was detectable at baseline but low amounts of the unconjugated compound could be detected with an average maximum of 0.8 nmol/L at about 1 h after ingestion. The data demonstrate that naringenin chalcone is bioavailable in humans from cherry tomatoes as a dietary source. However, availability is poor and intramolecular cyclisation as well as extended metabolism likely contribute to the inactivation of the reactive alpha-beta unsaturated reactive center as well as the excretion of the biologically active molecule, respectively.

Synthesis and antioxidant activity of 3-(3,4-dihydroxyphenyl)glyceric acid. Monomer of a biologically active polyether isolated from Symphytum asperum and S. caucasicum

Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
M Merlani ◽  
V Barbakadze ◽  
L Gogilashvili ◽  
L Amiranashvili ◽  
K Mulkijanyan ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Biologically Active ◽  
Glyceric Acid

Biologically active flavonoid glycosides from Horwoodia dicksoniae Turrill

Planta Medica ◽  
2011 ◽  
Vol 77 (12) ◽  
Author(s):  
GA Fawzy ◽  
AM Al Taweel ◽  
NA Abdelbaky ◽  
MS Marzouk
Keyword(s):  
Biologically Active ◽  
Flavonoid Glycosides

Biologically Active Phenolic Metabolites from Asphodelus microcarpus

Planta Medica ◽  
2013 ◽  
Vol 79 (10) ◽  
Author(s):  
MM Ghoneim ◽  
AA El-Hela ◽  
AEI Mohammad ◽  
SJ Cutler ◽  
SA Ross
Keyword(s):  
Biologically Active ◽  
Phenolic Metabolites ◽  
Asphodelus Microcarpus
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