Enzymatic Preparation of 2′–5′,3′–5′-Cyclic Dinucleotides, Their Binding Properties to Stimulator of Interferon Genes Adaptor Protein, and Structure/Activity Correlations

2019 ◽  
Vol 62 (23) ◽  
pp. 10676-10690 ◽  
Author(s):  
Barbora Novotná ◽  
Lenka Vaneková ◽  
Martin Zavřel ◽  
Miloš Buděšínský ◽  
Milan Dejmek ◽  
...  
Keyword(s):  
Adaptor Protein ◽  
Enzymatic Preparation ◽  
Binding Properties ◽  
Structure Activity ◽  
Cyclic Dinucleotides

Quantifying Target Occupancy of Small Molecules Within Living Cells

2020 ◽  
Vol 89 (1) ◽  
pp. 557-581 ◽  
Author(s):  
M.B. Robers ◽  
R. Friedman-Ohana ◽  
K.V.M. Huber ◽  
L. Kilpatrick ◽  
J.D. Vasta ◽  
...  
Keyword(s):  
Cultured Cells ◽  
Drug Efficacy ◽  
Living Cells ◽  
Drug Binding ◽  
Therapeutic Window ◽  
Target Engagement ◽  
Binding Properties ◽  
Structure Activity ◽  
Sar Analysis ◽  
Kinetics Of

The binding affinity and kinetics of target engagement are fundamental to establishing structure–activity relationships (SARs) for prospective therapeutic agents. Enhancing these binding parameters for operative targets, while minimizing binding to off-target sites, can translate to improved drug efficacy and a widened therapeutic window. Compound activity is typically assessed through modulation of an observed phenotype in cultured cells. Quantifying the corresponding binding properties under common cellular conditions can provide more meaningful interpretation of the cellular SAR analysis. Consequently, methods for assessing drug binding in living cells have advanced and are now integral to medicinal chemistry workflows. In this review, we survey key technological advancements that support quantitative assessments of target occupancy in cultured cells, emphasizing generalizable methodologies able to deliver analytical precision that heretofore required reductionist biochemical approaches.

scholarly journals Assessment of the Optimum Linker Tethering Site of Alternariol Haptens for Antibody Generation and Immunoassay Development

Toxins ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 883
Author(s):  
Luis G. Addante-Moya ◽  
Antonio Abad-Somovilla ◽  
Antonio Abad-Fuentes ◽  
Consuelo Agulló ◽  
Josep V. Mercader
Keyword(s):  
Total Synthesis ◽  
Monomethyl Ether ◽  
Alternariol Monomethyl Ether ◽  
Binding Properties ◽  
High Affinity ◽  
Structure Activity ◽  
Highly Sensitive ◽  
Alternaria Mycotoxins ◽  
Mycotoxin Analysis ◽  
First Time

Immunochemical methods for mycotoxin analysis require antigens with well-defined structures and antibodies with outstanding binding properties. Immunoreagents for the mycotoxins alternariol and/or alternariol monomethyl ether have typically been obtained with chemically uncharacterized haptens, and antigen conjugates have most likely been prepared with mixtures of functionalized molecules. For the first time, total synthesis was performed, in the present study, to obtain two haptens with opposite linker attachment locations. The functionalized synthetic haptens were purified and deeply characterized by different spectrometric methods, allowing the preparation of bioconjugates with unequivocal structures. Direct and indirect competitive enzyme-linked immunosorbent assays, using homologous and heterologous conjugates, were employed to extensively evaluate the generated immunoreagents. Antibodies with high affinity were raised from conjugates of both haptens, and a structure-activity relationship between the synthetic haptens and the specificity of the generated antibodies could be established. These results pave the way for the development of novel highly sensitive immunoassays selective of one or two of these Alternaria mycotoxins.

scholarly journals Enzymatic Preparation and Structure-activity Relationship of Sesaminol

2021 ◽  
Author(s):  
Jinhong Gao ◽  
Ruidan Wang ◽  
Xin Lu ◽  
Cong Jia ◽  
Qiang Sun ◽  
...  
Keyword(s):  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Enzymatic Preparation ◽  
Structure Activity ◽  
Relationship Of
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