Analysis of fungal cyclopentenone derivatives from Hygrophorus spp. by liquid chromatography/electrospray-tandem mass spectrometry

Fruitbodies of the genus Hygrophorus (Basidiomycetes) contain a series of anti-biologically active compounds. These substances named hygrophorones possess a cyclopentenone skeleton. LC/ESI-MS/MS presents a valuable tool for the identification of such compounds. The mass spectral behaviour of typical selected members of this group under positive and negative ion electrospray conditions is discussed. Using the ESI collision-induced dissociation (CID) mass spectra of the [M + H]+ and [M - H]- ions, respectively, the compounds can be classified with respect to the substitution pattern at the cyclopentenone ring and the type of oxygenation at C-6 (hydroxy/acetoxy or oxo function) of the side chain. The elemental composition of the fragment ions was determined by ESI-QqTOF measurements. Thus, in case of the negative ion CID mass spectra an unusual loss of CO2 from the deprotonated molecular ions could be observed.     

Modeling and active site refinement for G protein-coupled receptors: application to the β-2 adrenergic receptor

It is well known that G protein-coupled receptors are prime targets for drug discovery. At the present time there is only one protein from this class that has an X-ray crystal structure, bovine rhodopsin. Crystal structures of rhodopsin have become invaluable templates for the modeling of class-A G protein-coupled receptors as they likely represent the overall topology of this family of proteins. However, because of low sequence homology within the class and the inherent mobility of integral membrane proteins, it is unlikely that this single structural template reflects the ensemble of conformations accessible for any given receptor. We have devised a procedure based upon comparative modeling that uses induced fit modeling coupled with binding site expansion. The modeling protocol enables an ensemble approach to binding mode prediction. The utility of models for β-2 adrenergic receptor will be discussed.