Systematic Targeting of Protein-Protein Interactions.
Over the past decade, protein-protein interactions (PPIs) have gone from being neglected as 'undruggable' to being considered attractive targets for the development of therapeutics. Recent advances in computational analysis, fragment-based screening, and molecular design have revealed promising strategies to address the basic molecular recognition challenge: how to target large protein surfaces with specificity. Several systematic and complementary workflows have been developed to yield successful inhibitors of PPIs. Here we review the major contemporary approaches utilized for the discovery of inhibitors and focus on a structure-based workflow, from the selection of a biological target to design.
Department of Chemistry, New York University, New York, NY 10003, USA.
Ashley E
AE
Modell
Department of Chemistry, New York University, New York, NY 10003, USA.
Sarah L
SL
Blosser
Department of Chemistry, New York University, New York, NY 10003, USA.
Paramjit S
PS
Arora
D000818:Animals; D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D058990:Molecular Targeted Therapy; D060066:Protein Interaction Maps; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013329:Structure-Activity Relationship
D011506:Proteins
fragment-based design; inhibitors; protein-domain mimics; protein–protein interactions; rational design; screening