| Products/Services Used | Details | Operation |
|---|---|---|
| Peptide Synthesis | 5-HT. SERT was eluted with 150 mM NaCl, 20 mM HEPES pH 7.50, 0.1% (w/v) DDM, 0.01% (w/v) CHS,, 3 mM 5-HT, 1 mM EDTA, and 0.2 mg/mL protein C peptide (Genscript). Monodisperse SERT was purified by size-exclusion chromatography (SEC) in buffer comprised of 50 mM NaCl, 20 mM HEPES pH 7.50, 0.1% (w/v) DDM, 0.01% | Get A Quote |
Polypharmacological molecules are attractive for complex illnesses. Here, we explored large library docking for joint activity against target pairs. Retrospectively, as libraries grew, so too did the number of likely dual-activity molecules. In prospective docking of a 900-million molecule library against three target pairs ( 2A /SERT, MOR/SERT, and 2A /MOR), we sought analgesic compounds. Both the 2A /SERT and SERT/MOR campaigns led to dual binders with low M to high nM activities with high hit rates; tetrahydropyridines from the 2A /SERT campaign were also active against 5-HT 2A . However, even though cryo-EM structures confirmed the docking-predicted poses, optimization struggled to improve potency. Still, i... More
