title: Identification of inhibitors of biological interactions involving intrinsically disordered proteins.
abstract: Protein-protein interactions involving disordered partners have unique features and represent prominent targets in drug discovery processes. Intrinsically Disordered Proteins (IDPs) are involved in cellular regulation, signaling and control: they bind to multiple partners and these high-specificity/low-affinity interactions play crucial roles in many human diseases. Disordered regions, terminal tails and flexible linkers are particularly abundant in DNA-binding proteins and play crucial roles in the affinity and specificity of DNA recognizing processes. Protein complexes involving IDPs are short-lived and typically involve short amino acid stretches bearing few "hot spots", thus the identification of molecules able to modulate them can produce important lead compounds: in this scenario peptides and/or peptidomimetics, deriving from structure-based, combinatorial or protein dissection approaches, can play a key role as hit compounds. Here, we propose a panoramic review of the structural features of IDPs and how they regulate molecular recognition mechanisms focusing attention on recently reported drug-design strategies in the field of IDPs.
authors: Department of Pharmacy, Centro Interuniversitario di Ricerca sui Peptidi Bioattivi (CIRPEB), University of Naples "Federico II", DFM-Scarl, 80134 Naples, Italy. daniela.marasco@unina.it.
authors: Daniela
authors: D
authors: Marasco
authors: Department of Pharmacy, Centro Interuniversitario di Ricerca sui Peptidi Bioattivi (CIRPEB), University of Naples "Federico II", DFM-Scarl, 80134 Naples, Italy. liana.sco@gmail.com.
authors: Pasqualina Liana
authors: PL
authors: Scognamiglio
mesh_terms: D004268:DNA-Binding Proteins / Q000737:chemistry; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D064267:Intrinsically Disordered Proteins / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011485:Protein Binding / Q000187:drug effects
chemical_list: D004268:DNA-Binding Proteins; D064267:Intrinsically Disordered Proteins; D004364:Pharmaceutical Preparations