The Use of a Combination of RDC and Chiroptical Spectroscopy for Determination of the Absolute Configuration of Fusariumin A from the Fungus Fusarium sp.

A new alkylpyrrole derivative,fusariumin A(1),was isolated from the culture broth of the fungus Fusarium sp.The absolute configuration of fuasiumin A has been established as(2'R,3'R)using a combination of RDC(residual dipolar coupling)-based NMR and DFT-supported chiroptical spectroscopy.It is worth to note that in this study without the aid of the RDC analysis,an unambiguous determination of configuration and conformation was not feasible due to the excessive conformational possibilities of this open-chain compound.

Targeting α-synuclein by PD03 AFFITOPE■ and Anle 138b rescues neurodegenerative pathology in a model of multiple system atrophy:clinical relevance

Background:Misfolded oligomeric α-synuclein plays a pivotal role in the pathogenesis of a-synucleinopathies including Parkinson's disease and multiple system atrophy,and its detection parallels activation of microglia and a loss of neurons in the substantia nigra pars compacta.Here we aimed to analyze the therapeutic efficacy of PD03,a new AFFITOPE■ immunotherapy approach,either alone or in combination with Anle138b,in a PLP-α-syn mouse model.Methods:The PLP-α-syn mice were treated with PD03 immunotherapy,Anle138b,or a combination of two.Five months after study initiation,the mice underwent behavioral testing and were sacrificed for neuropathological analysis.The treatment groups were compared to the vehicle group with regard to motor performance,nigral neuronal loss,microglial activation and α-synuclein pathology.Results:The PLP-α-syn mice receiving the PD03 or Anle138b single therapy showed improvement of gait deficits and preservation of nigral dopaminergic neurons associated with the reduced α-synuclein oligomer levels and decreased microglial activation.The combined therapy with Anle138b and PD03 resulted in lower lgG binding in the brain as compared to the single immunotherapy with PD03.Conclusions:PD03 and Anle138b can selectively target oligomeric α-synuclein,resulting in attenuation of neurodegeneration in the PLP-α-syn mice.Both approaches are potential therapies that should be developed further for disease modification in α-synucleinopathies.