scholarly journals 6-Nitro-7-tosylquinazolin-4(3H)-one

Molbank ◽  
10.3390/m1168 ◽  
2020 ◽  
Vol 2020 (4) ◽  
pp. M1168
Author(s):  
Thi Ngoc Nguyen ◽  
Thi Phuong Thuy Tran ◽  
Thi Hoang Mai Vu ◽  
Hoa Binh Nguyen ◽  
Nguyet Suong Huyen Dao ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Quantum Coherence ◽  
Multiple Bond ◽  
Growth Factor Receptor ◽  
Functional Materials ◽  
Building Blocks ◽  
Correlation Spectroscopy ◽  
Biologically Active ◽  
Ft Ir ◽  
Epidermal Growth

Sulfones are important building blocks in the construction of biologically active molecules or functional materials. The sulfonyl functional group in sulfones is so versatile that it can act as either a nucleophile, an electrophile, or a radical in different organic reactions. Recently, quinazoline sulfones have been used to build asymmetrical ether derivatives as inhibitors of signaling pathways governed by tyrosine kinases and the epidermal growth factor-receptor. In this paper, we report a facile synthesis of a novel quinazoline sulfone, 6-nitro-7-tosylquinazolin-4(3H)-one (III), using the modified protocol from 7-chloro-6-nitroquinazolin-4(3H)-one (I) and sodium p-toluenesulfinate (II). The structure of the title compound III was determined using mass-spectrometry, FT-IR, 1H-NMR, 13C-NMR, DEPT, HSQC (Heteronuclear single quantum coherence), HMBC (Heteronuclear Multiple Bond Correlation Spectroscopy) spectroscopies, and PXRD analysis.

scholarly journals An Electrostatic Engine Model for Autoinhibition and Activation of the Epidermal Growth Factor Receptor (EGFR/ErbB) Family

2005 ◽  
Vol 126 (1) ◽  
pp. 41-53 ◽  
Author(s):  
Stuart McLaughlin ◽  
Steven O. Smith ◽  
Michael J. Hayman ◽  
Diana Murray
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinases ◽  
Structural Model ◽  
Growth Factor Receptor ◽  
Kinase Domain ◽  
Correlation Spectroscopy ◽  
Erbb Family ◽  
Epidermal Growth

We propose a new mechanism to explain autoinhibition of the epidermal growth factor receptor (EGFR/ErbB) family of receptor tyrosine kinases based on a structural model that postulates both their juxtamembrane and protein tyrosine kinase domains bind electrostatically to acidic lipids in the plasma membrane, restricting access of the kinase domain to substrate tyrosines. Ligand-induced dimerization promotes partial trans autophosphorylation of ErbB1, leading to a rapid rise in intracellular [Ca2+] that can activate calmodulin. We postulate the Ca2+/calmodulin complex binds rapidly to residues 645–660 of the juxtamembrane domain, reversing its net charge from +8 to −8 and repelling it from the negatively charged inner leaflet of the membrane. The repulsion has two consequences: it releases electrostatically sequestered phosphatidylinositol 4,5-bisphosphate (PIP2), and it disengages the kinase domain from the membrane, allowing it to become fully active and phosphorylate an adjacent ErbB molecule or other substrate. We tested various aspects of the model by measuring ErbB juxtamembrane peptide binding to phospholipid vesicles using both a centrifugation assay and fluorescence correlation spectroscopy; analyzing the kinetics of interactions between ErbB peptides, membranes, and Ca2+/calmodulin using fluorescence stop flow; assessing ErbB1 activation in Cos1 cells; measuring fluorescence resonance energy transfer between ErbB peptides and PIP2; and making theoretical electrostatic calculations on atomic models of membranes and ErbB juxtamembrane and kinase domains.

Two-dimensional NMR studies of acrylate copolymers

2009 ◽  
Vol 81 (3) ◽  
pp. 389-415 ◽  
Author(s):  
A. S. Brar ◽  
Ashok Kumar Goyal ◽  
Sunita Hooda
Keyword(s):  
Methyl Methacrylate ◽  
Methyl Acrylate ◽  
Quantum Coherence ◽  
Multiple Bond ◽  
Microstructural Analysis ◽  
2D Nmr ◽  
Correlation Spectroscopy ◽  
Nmr Studies ◽  
Poly Methyl Methacrylate ◽  
Nmr Study

High-resolution NMR spectroscopy is the most versatile, reliable, and generally acceptable technique for the determination of the microstructure of polymers. 2D NMR techniques, along with 1D NMR, have more potential to study absolute configurational assignments and sequence distribution of copolymers. Physical and chemical properties of polymers are influenced fundamentally by their microstructure. We discuss the detailed microstructure analysis of a large number of homopolymers, copolymers, and terpolymers. 2D NMR study of poly(methyl methacrylate) (PMMA), poly(methyl acrylate) (PMA), and poly(methacrylonitrile) (PMAN) is discussed in this article. In addition to homopolymers, 2D heteronuclear single-quantum coherence (HSQC), total correlation spectroscopy (TOCSY), and heteronuclear multiple-bond correlation (HMBC) study of different copolymers such as poly(methyl methacrylate-co-methyl acrylate), poly(styrene-co-methyl methacrylate), and poly(methyl methacrylate-co-methacrylonitrile) have also been reported here. This in turn helps in microstructural analysis of terpolymers such as poly(methacrylonitrile-co-styrene-co-methyl methacrylate), poly(acrylonitrile-co-methyl methacrylate-co-methyl acrylate), and poly(ethylene-co-vinyl acetate-co-carbon monoxide).

An epidermal growth factor receptor/ret chimera generates mitogenic and transforming signals: evidence for a ret-specific signaling pathway

1994 ◽  
Vol 14 (1) ◽  
pp. 663-675
Author(s):  
M Santoro ◽  
W T Wong ◽  
P Aroca ◽  
E Santos ◽  
B Matoskova ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinases ◽  
Mammalian Cells ◽  
Egf Receptor ◽  
Biological Effects ◽  
Ectopic Expression ◽  
Growth Factor Receptor ◽  
Dependent Signal ◽  
Epidermal Growth

A chimeric expression vector which encoded for a molecule encompassing the extracellular domain of the epidermal growth factor (EGF) receptor (EGFR) and the intracellular domain of the ret kinase (EGFR/ret chimera) was generated. Upon ectopic expression in mammalian cells, the EGFR/ret chimera was correctly synthesized and transported to the cell surface, where it was shown capable of binding EGF and transducing an EGF-dependent signal intracellularly. Thus, the EGFR/ret chimera allows us to study the biological effects and biochemical activities of the ret kinase under controlled conditions of activation. Comparative analysis of the growth-promoting activity of the EGFR/ret chimera expressed in fibroblastic or hematopoietic cells revealed a biological phenotype clearly distinguishable from that of the EGFR, indicating that the two kinases couple with mitogenic pathways which are different to some extent. Analysis of biochemical pathways implicated in the transduction of mitogenic signals also evidenced significant differences between the ret kinase and other receptor tyrosine kinases. Thus, the sum of our results indicates the existence of a ret-specific pathway of mitogenic signaling.

scholarly journals Quantifying the strength of heterointeractions among receptor tyrosine kinases from different subfamilies: Implications for cell signaling

2020 ◽  
Vol 295 (29) ◽  
pp. 9917-9933 ◽  
Author(s):  
Michael D. Paul ◽  
Hana N. Grubb ◽  
Kalina Hristova
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Eph Receptor ◽  
Vital Cell ◽  
Cell Processes ◽  
Epidermal Growth ◽  
Endothelial Growth Factor

Receptor tyrosine kinases (RTKs) are single-pass membrane proteins that control vital cell processes such as cell growth, survival, and differentiation. There is a growing body of evidence that RTKs from different subfamilies can interact and that these diverse interactions can have important biological consequences. However, these heterointeractions are often ignored, and their strengths are unknown. In this work, we studied the heterointeractions of nine RTK pairs, epidermal growth factor receptor (EGFR)–EPH receptor A2 (EPHA2), EGFR–vascular endothelial growth factor receptor 2 (VEGFR2), EPHA2–VEGFR2, EPHA2–fibroblast growth factor receptor 1 (FGFR1), EPHA2–FGFR2, EPHA2–FGFR3, VEGFR2–FGFR1, VEGFR2–FGFR2, and VEGFR2–FGFR3, using a FRET-based method. Surprisingly, we found that RTK heterodimerization and homodimerization strengths can be similar, underscoring the significance of RTK heterointeractions in signaling. We discuss how these heterointeractions can contribute to the complexity of RTK signal transduction, and we highlight the utility of quantitative FRET for probing multiple interactions in the plasma membrane.

scholarly journals Signal co-operation between integrins and other receptor systems

2009 ◽  
Vol 418 (3) ◽  
pp. 491-506 ◽  
Author(s):  
Charles H. Streuli ◽  
Nasreen Akhtar
Keyword(s):  
Cell Fate ◽  
Tyrosine Kinases ◽  
Spatial Organization ◽  
Growth Factor Receptor ◽  
Cellular Processes ◽  
Extracellular Signals ◽  
Β1 Integrins ◽  
Α6β4 Integrin ◽  
Epidermal Growth ◽  
Adhesive Interactions

The multicellular nature of metazoans means that all cellular processes need to be tuned by adhesive interactions between cells and their local microenvironment. The spatial organization of cells within tissues requires sophisticated networks of extracellular signals to control their survival and proliferation, movements and positioning, and differentiated function. These cellular characteristics are mediated by multiple inputs from adhesion systems in combination with soluble and developmental signals. In the present review we explore how one class of adhesion receptor, the integrins, co-operate with other types of receptor to control diverse aspects of cell fate. In particular we discuss: (i) how β3 and β1 integrins work together with growth factors to control angiogenesis; (ii) how α6β4 integrin co-operates with receptor tyrosine kinases in normal epithelial function and cancer; (iii) the interplay between β1 integrins and EGF (epidermal growth factor) receptor; (iv) signal integration connecting integrins and cytokine receptors for interleukins, prolactin and interferons; and (v) how integrins and syndecans co-operate in cell migration.

scholarly journals Integration of the Extranuclear and Nuclear Actions of Estrogen

2005 ◽  
Vol 19 (8) ◽  
pp. 1951-1959 ◽  
Author(s):  
Ellis R. Levin
Keyword(s):  
Signal Transduction ◽  
Growth Factor ◽  
Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Sex Steroid ◽  
Phosphatidylinositol 3 Kinase ◽  
Epidermal Growth ◽  
Small Pool ◽  
Physiological Outcomes ◽  
Nuclear Effects

Abstract Estrogen receptors (ERs) are localized to many sites within the cell, potentially contributing to overall estrogen action. In the nucleus, estrogen mainly modulates gene transcription, and the resulting protein products determine the cell biological actions of the sex steroid. In addition, a small pool of ERs localize to the plasma membrane and signal mainly though coupling, directly or indirectly, to G proteins. In response to steroid, signal transduction modulates both nontranscriptional and transcriptional events and impacts both the rapid and more prolonged actions of estrogen. Cross-talk from membrane-localized ERs to nuclear ERs can be mediated through growth factor receptor tyrosine kinases, such as epidermal growth factor receptor and IGF-I receptor. Growth factor receptors enact signal transduction to kinases such as ERK and phosphatidylinositol 3-kinase that phosphorylate and activate nuclear ERs, and this can also occur in the absence of sex steroid. A complex relationship between the membrane and nuclear effects of estrogen also involves membrane-initiated phosphorylation of coactivators, recruiting these proteins to the nuclear transcriptosome. Finally, large pools of cytoplasmic ERs exist, and some are localized to mitochondria. The integration of sex steroid effects at distinct cellular locations of its receptor leads to important cellular physiological outcomes and are manifest in both reproductive and nonreproductive organs.

The effect of cell–ECM adhesion on signalling via the ErbB family of growth factor receptors

2011 ◽  
Vol 39 (2) ◽  
pp. 568-573 ◽  
Author(s):  
Xanthippi Alexi ◽  
Fedor Berditchevski ◽  
Elena Odintsova
Keyword(s):  
Growth Factor ◽  
Critical Role ◽  
Growth Factor Receptor ◽  
Growth Factor Receptors ◽  
Building Blocks ◽  
Erbb Receptors ◽  
Cellular Interactions ◽  
Transmembrane Receptors ◽  
Erbb Family ◽  
Epidermal Growth

Integrins and growth factor receptors of the ErbB family are involved in the regulation of cellular interactions with the extracellular microenvironment. Cross-talk between these two groups of transmembrane receptors is essential for cellular responses and can be regulated through the formation of multimolecular complexes. Tetraspanins as facilitators and building blocks of specialized microdomains may be involved in this process. In the present study, we demonstrated that, in contrast with previous reports, integrin-mediated adhesion did not stimulate ligand-independent activation of ErbB receptors in epithelial cells. However, integrin-dependent adhesion potentiated ligand-induced activation of EGFR (epidermal growth factor receptor) and ErbB2 and facilitated receptor homo- and hetero-dimerization. The actin cytoskeleton appeared to play a critical role in this phenomenon.

scholarly journals RNA Interference Screen Identifies Usp18 as a Regulator of Epidermal Growth Factor Receptor Synthesis

2009 ◽  
Vol 20 (6) ◽  
pp. 1833-1844 ◽  
Author(s):  
Jason E. Duex ◽  
Alexander Sorkin
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Mrna Translation ◽  
Small Interfering Rnas ◽  
Catalytic Cysteine ◽  
Elevated Expression ◽  
Epidermal Growth

Elevated expression of epidermal growth factor receptor (EGFR) contributes to the progression of many types of cancer. Therefore, we developed a high-throughput screen to identify proteins that regulate the levels of EGFR in squamous cell carcinoma. Knocking down various ubiquitination-related genes with small interfering RNAs led to the identification of several novel genes involved in this process. One of these genes, Usp18, is a member of the ubiquitin-specific protease family. We found that knockdown of Usp18 in several cell lines reduced expression levels of EGFR by 50–80%, whereas the levels of other receptor tyrosine kinases remained unchanged. Overexpression of Usp18 elevated EGFR levels in a manner requiring the catalytic cysteine of Usp18. Analysis of metabolically radiolabeled cells showed that the rate of EGFR protein synthesis was reduced up to fourfold in the absence of Usp18. Interestingly, this dramatic reduction occurred despite no change in the levels of EGFR mRNA. This suggests that depletion of Usp18 inhibited EGFR mRNA translation. In fact, this inhibition required the presence of native 5′ and 3′ untranslated region sequences on EGFR mRNA. Together, our data provide evidence for the novel mechanism of EGFR regulation at the translational step of receptor synthesis.

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