1. Design and synthesis of bombykol analogues for probing pheromone-binding protein–ligand interactions
- Author
-
Jan Doubský, Alexandr Muck, P. Nešněrová, V. Klusák, Madina Mansourova, and Aleš Svatoš
- Subjects
Stereochemistry ,Ligand ,Ligand binding assay ,Organic Chemistry ,Sonogashira coupling ,Biochemistry ,Bombykol ,Dissociation constant ,chemistry.chemical_compound ,Hydroboration ,chemistry ,Ab initio quantum chemistry methods ,Drug Discovery ,Pheromone binding protein - Abstract
Mono-, difluorinated, and thioanalogues of Bombyx mori female sex pheromones (bombykol, 1 ) were designed according to the ab initio calculations. These rationally designated analogues were synthesized using hydroboration and Sonogashira coupling strategy via (5 E ,7 Z )-undecadien-1-ol ( 10 ) as a common intermediate. A new simplified binding assay based on nanoLC-linear ion trap ESI-MS for quantifying complexation of the B. mori pheromone-binding protein (BmPBP) with native ( 1 ) and prepared analogues was developed. The binding properties of native 1 and thioanalogue 4 with PBP were studied in detail. The dissociation constant ( K D ) of 1 and 4 was determined to be 2.1×10 −6 M and 2.4×10 −6 M, respectively. The similar values for both ligands correlated with ab initio calculations. The new binding assay could be used to determine the K D of other PBPs.
- Published
- 2009