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公开(公告)号：US10829515B2
公开(公告)日：2020-11-10
申请号：US16307200
申请日：2017-06-06
发明人： Ashwin Chari , Holger Stark , Jil Schrader , Fabian Henneberg
摘要： The present invention relates in a first aspect to a method for the purification of biological macromolecular complexes. Typically, no chromatography steps are applied. That is, the present invention relates to a method for the purification of biological macromolecular complexes Furthermore, the present invention relates to a method for crystallization of biological macromolecular complexes comprising the step of purification as described followed by crystallization in a reservoir solution containing a water-soluble polymer. Furthermore, purified biological macromolecular complexes obtainable by the method according to the present invention are provided as well as crystallized biological macromolecular complexes. Finally, a method for determining the suitability of a candidate compound for inhibiting the 20S proteasome of an individual is provided. Said method is particularly useful in personalized medicine identifying suitable inhibitors of the 20S proteasome in individuals for treating, ameliorating or preventing a cancer, an autoimmune disease, a muscular dystrophy, emphysema or cachexia accompanying cancer or AIDS.
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公开(公告)号：US11345724B2
公开(公告)日：2022-05-31
申请号：US16305693
申请日：2017-06-06
发明人： Ashwin Chari , Holger Stark , Jil Schrader , Fabian Henneberg
摘要： The present invention relates to a compound of formula (I), wherein X is C═O, C═S or B—OH; Y is an electrophile and Z is a leaving group, or Y═Z is an electrophile; R1 comprises or consists of (a) (i) a first group binding to a proteolytic site of a proteasome, the first group being bound to X; and (ii) optionally a second group enhancing delivery; or (b) a group binding between subunits β1 and β2 of a proteasome; R2 and R3 are independently selected from H, methyl, methoxy, ethyl, ethenyl, ethynyl and cyano, wherein methyl and ethyl may be substituted with OH or halogen.
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