Unraveling phosphodiesterase surfaces. Identification of phosphodiesterase 7 allosteric modulation cavities.
The last findings of our group by using chemical genetic approaches have shown that PDE7 is an interesting target in neurodegenerative diseases. The following step in this travel to unravel PDE7 is the design of more selective inhibitors. In this sense we have proposed to perform an analysis of PDE7 surface to identify possible allosteric sites following by a docking study of different PDE7 inhibitors synthesized by our group. Thanks to these studies we have proved the existence of allosteric sites in PDE7 and we have been able to explain the binding modes of the employed PDE7 inhibitors.
Instituto de Química Médica (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain.
Miriam
M
Redondo
Ignacio
I
Soteras
José
J
Brea
Alejandro
A
González-García
María Isabel
MI
Cadavid
María Isabel
MI
Loza
Ana
A
Martinez
Carmen
C
Gil
Nuria E
NE
Campillo
D000494:Allosteric Regulation / Q000187:drug effects; D000495:Allosteric Site / Q000187:drug effects; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013499:Surface Properties
D010726:Phosphodiesterase Inhibitors; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7; C517458:PDE7A protein, human
Allosteric sites; Docking; Neurodegeneration; PDE7; Surface study