A5073561395- Pharmacological Receptor Mechanisms and Effects
- Neuropeptides and Animal Physiology
- Receptor Mechanisms and Signaling
- Fluorine in Organic Chemistry
- Advanced biosensing and bioanalysis techniques
- DNA and Nucleic Acid Chemistry
- Click Chemistry and Applications
- Radical Photochemical Reactions
- Chemical Synthesis and Analysis
- Synthesis and Biological Evaluation
- Synthesis and Catalytic Reactions
- Sulfur-Based Synthesis Techniques
- Catalysis and Oxidation Reactions
- Mesoporous Materials and Catalysis
- Zeolite Catalysis and Synthesis
University of Kansas
2018-2022
University of North Carolina at Chapel Hill
2022
We describe a novel approach for screening fragments against protein that combines the sensitivity of DNA-encoded library technology with ability to explore what will bind. Each members consists fragment which is linked photoactivatable diazirine moiety. Split and pool synthesis each set linkers version reported here containing some 70k different compounds, an individual DNA code. Incubation sample followed by photoactivation, washing subsequent PCR sequencing allows hits be identified....
Thioethers have been widely found in biologically active compounds, including pharmaceuticals. In this report, a highly efficient approach to on-DNA construction of thioethers via Cu-promoted Ullmann cross-coupling between DNA-conjugated aryl iodides and thiols is developed. This methodology was demonstrated with medium high yields, without obvious DNA damage. reported reaction has strong potential for application DNA-encoded chemical library synthesis.
An efficient visible-light-induced alkylation of DNA-tagged quinoxaline-2-ones was described. The methodology demonstrated moderate-to-excellent conversions under mild conditions. reaction found to be tolerant with both N-protected α-amino acids and aliphatic carboxylic could applied the synthesis focused DNA-encoded quinoxalin-2-one libraries.
Focused modification of a sulfonamide-based kappa opioid receptor (KOR) antagonist series previously reported by this laboratory was investigated. A total 32 analogues were prepared to explore linker replacement, constraint manipulation, and aryl group or amine substitution. All assayed for KOR activity, the initial lead compound assessed in vivo CNS penetration. The most improved analogue possessed 4-fold increase potency (IC50 = 18.9 ± 4.4 nM) compared with 83.5 20 from an earlier work....