Search results for "Structure-Activity Relationship"
showing 10 items of 743 documents
Assessment of temperature effects on beta-aggregation of native and glycated albumin by FTIR spectroscopy and PAGE: relations between structural chan…
2007
Abstract Structural modifications of bovine serum albumin (BSA) induced by heating, and the involvement of glycation of albumin in such processing were studied by using Fourier transform infrared spectroscopy (FTIR) and polyacrylamide gel electrophoresis (PAGE). For native BSA, heating treatments gave rise to β structures which were amplified to the detriment of α-helix form, and which were associated with increased aggregation. A very high correlation was obtained between FTIR Amide I band evolution and aggregation rate parameters, showing the contribution of β-form in aggregates formation. We further assessed the effect of glycation on protein sensibility to heating treatments. A reductio…
On the Relationship between Jetted Inks and Printed Biopatterns:Molecular-Thin Functional Microarrays of Glucose Oxidase
2009
Arrays of circular spots of glucose oxidase have been obtained on functionalized silicon oxide by piezoelectric inkjet printing and the enzymatic activity toward glucose recognition has been monitored. The addition of glycerol to the molecular ink allows to obtain high spot definition and resolution (tens of micrometers wide; one molecule tall), but in spite of its well-known structural stabilizing properties, in dynamic conditions it may lead to increased protein stresses. The jetting voltage and pulse length have been found to be critical factors for both activity retention and pattern definition. High voltages and pulse lengths results in stress effects along with the loss of activity, w…
Stereospecific interaction of bicuculline with specific [3H]strychnine binding to rat spinal cord synaptosomal membranes
1980
The gamma-aminobutyric acid (GABA) antagonist (+/-)-bicuculline inhibits specific [3H]strychnine binding to postsynaptic glycine receptor sites in rat spinal cord synaptosomal membranes with an inhibition constant of about 5 microM, which is fairly similar to its inhibition constant reported for the GABA receptor. This effect is highly stereospecific, since the affinity of (-)-bicuculline for the specific [3H]strychnine binding sites is more than ten times less than that of the pharmacologically active (+)-bicuculline. Besides an unspecific effect at the glycine receptor, the results could suggest that the glycine and the GABA receptors are located close together in spinal cord membranes, s…
Design, Synthesis and Biological Evaluation of 7-Chloro-9
2019
Glycogen synthase kinase-3β (GSK-3β) represents a relevant drug target for the treatment of neurodegenerative pathologies including Alzheimer’s disease. We herein report on the optimization of a novel class of GSK-3β inhibitors based on the tofacitinib-derived screen hit 3-((3R,4R)-3-((7-chloro-9H-pyrimido[4,5-b]indol-4-yl)(methyl)amino)-4-methylpiperidin-1-yl)-3-oxopropanenitrile (1). We synthesized a series of 19 novel 7-chloro-9H-pyrimido[4,5-b]indole-based derivatives and studied their structure–activity relationships with focus on the cyanoacetyl piperidine moiety. We unveiled the crucial role of the nitrile group and its importance for the activity of this compound series. A successfu…
Fluorinated glycosyl amino acids for mucin-like glycopeptide antigen analogues.
2010
The aberrant glycosylation profiles of mucin glycoproteins on epithelial tumour cells represent attractive target structures for the development of immunotherapy against cancer. Mucin-type glycopeptides have been successfully investigated as molecularly defined vaccine prototypes for triggering humoral immunity but are susceptible to rapid in vivo degradation. As a potential means to enhance the bioavailabilities of the antigenic structures, hydrolysis-resistant carbohydrate analogues with fluorine substituents at positions C6, C2' and C6' were synthesised and incorporated into the tandem repeat sequence of the mucin MUC1. The resulting pseudo-glycopeptides can be used to elucidate the effe…
Porphyrin-bile acid conjugates: from saccharide recognition in the solution to the selective cancer cell fluorescence detection.
2008
This paper describes the preparation and use of conjugates of porphyrins and bile acids as ligands to bind to tumor expressed saccharides. Bile acid-porphyrin conjugates were tested for recognition of saccharides that are typically present on malignant tumor cells. Fluorescence microscopy, in vitro PDT cell killing, and PDT of subcutaneous 4T1 mouse tumors is reported. High selectivity for saccharide cancer markers and cancer cells was observed. This in vivo and in vitro study demonstrated high potential use for these compounds in targeted photodynamic therapy.
Ruthenium-arene complexes bearing naphthyl-substituted 1,3-dioxoindan-2-carboxamides ligands for G-quadruplex DNA recognition.
2019
Quadruplex nucleic acids – DNA/RNA secondary structures formed in guanine rich sequences – proved to have key roles in the biology of cancers and, as such, in recent years they emerged as promising targets for small molecules. Many reports demonstrated that metal complexes can effectively stabilize quadruplex structures, promoting telomerase inhibition, downregulation of the expression of cancer-related genes and ultimately cancer cell death. Although extensively explored as anticancer agents, studies on the ability of ruthenium arene complexes to interact with quadruplex nucleic acids are surprisingly almost unknown. Herein, we report on the synthesis and characterization of four novel Ru(…
Triterpenoid saponins from the roots of two Gypsophila species.
2013
Two triterpenoid saponins with two known ones have been isolated from the roots of Gypsophila arrostii var. nebulosa, and two new ones from the roots of Gypsophila bicolor. Their structures were established by extensive NMR and mass spectroscopic techniques as 3-O-β-d-galactopyranosyl-(1→2)-[β-d-xylopyranosyl-(1→3)]-β-d-glucuronopyranosylquillaic acid 28-O-β-d-xylopyranosyl-(1→4)-[β-d-glucopyranosyl-(1→3)]-α-l-rhamnopyranosyl-(1→2)-[β-d-glucopyranosyl-(1→4)]-β-d-fucopyranosyl ester (1), 3-O-β-d-galactopyranosyl-(1→2)-[β-d-xylopyranosyl-(1→3)]-β-d-glucuronopyranosylgypsogenin 28-O-β-d-xylopyranosyl-(1→4)-[β-d-glucopyranosyl-(1→3)]-α-l-rhamnopyranosyl-(1→2)-[β-d-glucopyranosyl-(1→4)]-β-d-fuco…
Highly Fluorinated 2,2′-Biphenols and Related Compounds: Relationship between Substitution Pattern and Herbicidal Activity
2013
A broad range of halogenated 2,2'-biphenols was tested for applicability as crop protection agents. The activity of these compounds toward four typical pest plants was observed after application by spraying of diluted solutions. Despite their rather simple structure, it was found that the studied compounds reveal a surprisingly high herbicidal impact. To gain a better understanding of the structure-activity relationship, specific sites of the molecule were chemically modified and the core structures thus gradually changed. The influence of the substitution pattern on the herbicidal properties is discussed, and conclusions on the active site of the biphenol structure are drawn. It was observ…
Myristylation is involved in intracellular retention of hepatitis B virus envelope proteins
1991
The envelope of hepatitis B virus contains three related proteins, one of which is myristylated. The nonmyristylated small and middle protein are assembled into empty envelope particles which are secreted from cells, whereas the myristylated large envelope protein is mainly found in complete virions and is not secreted in the absence of the nucleocapsid. The block to secretion can be partially overcome by mutation or deletion of the myristylation site. Creation of a myristyl attachment site in the small protein impairs the secretion of empty envelope particles but not their intracellular assembly. Myristylation may therefore play a crucial role in hepatitis B virus replication by channeling…