Where Electrophile Signaling and Covalent Ligand–Target Mining Converge

Interests in learning how to engineer most effective covalent ligands, identify novel functional targets, and define precise mechanism-of-action are rapidly growing in both academia and pharmaceutical industries. We here illuminate the establishment of a multifunctional platform that offers new capabilities to logically engineer covalent ligands and dissect 'on-target' bioactivity with precise biological context and precision hitherto inaccessible. Broadly aimed at non-specialist readers, this opinion piece is aimed to stoke the interest of emerging chemists and biologists/bioengineers, but the underlying technological and conceptual topicality is anticipated to also appeal to experts leading ligand–target mining, validation, and -discovery research programs.

Download Full-text

Development of a Selection Method for Discovering Irreversible (Covalent) Binders from a DNA-Encoded Library

SLAS DISCOVERY Advancing Life Sciences ◽

10.1177/2472555218808454 ◽

2018 ◽

Vol 24 (2) ◽

pp. 169-174 ◽

Cited By ~ 2

Author(s):

Zhengrong Zhu ◽

LaShadric C. Grady ◽

Yun Ding ◽

Kenneth E. Lind ◽

Christopher P. Davie ◽

...

Keyword(s):

Magnetic Beads ◽

Chemical Probes ◽

Lead Discovery ◽

3C Protease ◽

Discovery Research ◽

Drug Discovery Research ◽

Affinity Resin ◽

Covalent Ligands ◽

Developing Method ◽

Unique Mechanism

DNA-encoded libraries (DELs) have been broadly applied to identify chemical probes for target validation and lead discovery. To date, the main application of the DEL platform has been the identification of reversible ligands using multiple rounds of affinity selection. Irreversible (covalent) inhibition offers a unique mechanism of action for drug discovery research. In this study, we report a developing method of identifying irreversible (covalent) ligands from DELs. The new method was validated by using 3C protease (3CP) and on-DNA irreversible tool compounds (rupintrivir derivatives) spiked into a library at the same concentration as individual members of that library. After affinity selections against 3CP, the irreversible tool compounds were specifically enriched compared with the library members. In addition, we compared two immobilization methods and concluded that microscale columns packed with the appropriate affinity resin gave higher tool compound recovery than magnetic beads.

Download Full-text

Biological Properties of Some Volatile Phenylpropanoids

Natural Product Communications ◽

10.1177/1934578x1601101041 ◽

2016 ◽

Vol 11 (10) ◽

pp. 1934578X1601101 ◽

Cited By ~ 1

Author(s):

Radmila Ilijeva ◽

Gerhard Buchbauer

Keyword(s):

Clinical Trials ◽

Essential Oils ◽

Mechanism Of Action ◽

Biological Activities ◽

Biological Properties ◽

Anticancer Activities ◽

Pharmacological Activities ◽

Prevention And Treatment ◽

Pharmaceutical Industries ◽

Almost All

Plants and their extracts are the new field of interest for many scientists and also of some pharmaceutical industries. In order to provide more information for their usage in the prevention and treatment of diseases many clinical trials and researches are being carried out. In this review the biological activities and the mechanism of action of volatile phenylpropanoids (PPs) found in essential oils (EOs) are presented. The aim of this overview is to show that volatile PPs found in EOs can exert many of the biological activities which are generally attributed to EOs. Almost all of the PPs possess antimicrobial, anti-inflammatory and anticancer activities. These are related to the different substitution of the phenylpropane molecule. For each isolated group not only one, but more pharmacological activities can be credited.

Download Full-text