New spatial model of polypeptide containing a TPR motif, useful for identifying inhibitors of interaction between chaperone and Hop proteins, potential therapeutics

摘要

Spatial model of a polypeptide (I) having at least one amino acid (aa) sequence (II) of a TPR structural motif of a Hop protein, or a derivative of (II), is new. Independent claims are also included for the following: (1) crystal containing, per asymmetric unit of its unit cell, at least one (I) and optionally another compound; (2) preparing the crystals of (1); (3) compounds (III) that bind, as ligands, to a structural region of a Hop protein (or structurally related protein) by non-covalent interaction with the main and/or side chains of aa that are components of the TPR domain; (4) peptides (Ia), having the spatial model of (I), that can bind to a chaperone protein (CP) but are non-functional as regards adapter function; (5) identifying compounds (A) that inhibit interaction between CP and Hop proteins; (6) (A) identified by the method of (5); (7) representing the three-dimensional (3D) structure of a polypeptide of unknown structure but containing at least one TPR motif (or its derivative or complex), using the model of (I); (8) identifying compounds (A') that inhibit interaction between CP and polypeptides containing at least one TPR motif, or its derivatives; (9) pharmaceutical compositions containing (A) or (A'); (10) DNA sequences (IV) that encode a sequence that contains at least part of proteins TTC1 to 4, IRSP, SGT and KIAA0719; (11) amino acid sequences (V) encoded by (IV); and (12) pharmaceutical composition containing (V), their fragments or derivatives. - ACTIVITY : Cytostatic; virucide; immunosuppressive; antiinflammatory. No biological data is given. - MECHANISM OF ACTION : Inhibiting interaction between Hop and chaperone proteins.