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.

Identification of inhibitors of biological interactions involving intrinsically disordered proteins / Marasco, Daniela; Scognamiglio, PASQUALINA LIANA. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 16:4(2015), pp. 7394-412-7412. [10.3390/ijms16047394]

Identification of inhibitors of biological interactions involving intrinsically disordered proteins

MARASCO, DANIELA
Primo
Conceptualization
;
SCOGNAMIGLIO, PASQUALINA LIANA
Writing – Review & Editing
2015

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.
2015
Identification of inhibitors of biological interactions involving intrinsically disordered proteins / Marasco, Daniela; Scognamiglio, PASQUALINA LIANA. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 16:4(2015), pp. 7394-412-7412. [10.3390/ijms16047394]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/612648
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