Hybrid organic-inorganic inhibitors of a PDZ interaction that regulates the endocytic fate of CFTR.
Together strong: Cooperative binding of organic (see picture, red) and inorganic fragments provides a strategy for the potent inhibition of protein-protein interactions. By targeting specific Lewis basic side chains in peripheral regions of the binding site for coordination to a rhodium(II) center, the affinity of otherwise weak ligands is improved.
Department of Chemistry, Rice University, 6100 Main St., Houston, TX 77005, USA.
Rituparna
R
Kundu
Patrick R
PR
Cushing
Brian V
BV
Popp
Yu
Y
Zhao
Dean R
DR
Madden
Zachary T
ZT
Ball
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077614:Golgi Matrix Proteins; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D026901:Membrane Transport Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology; D054731:PDZ Domains / Q000187:drug effects*; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D012238:Rhodium / Q000737:chemistry* / Q000494:pharmacology*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C434484:GOPC protein, human; D000077614:Golgi Matrix Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009942:Organometallic Compounds; D010455:Peptides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D012238:Rhodium