Identifying protein stabilizing ligands using GroEL.
Over the past 5 years, it has become increasingly apparent to researchers that the initial promise and excitement of using gene replacement therapies to ameliorate folding diseases are still far from being broadly or easily applicable. Because a large number of human diseases are protein folding diseases (approximately 30 to 50%), many researchers now realize that more directed approaches to target and reverse the fundamental misfolding reactions preceding disease are highly feasible and offer the potential of developing more targeted drug therapies. This is also true with a large number of so called orphan protein folding diseases. The development of a broad-based general screening array method using the chaperonin as a detection platform will enable us to screen large chemical combinatorial libraries for specific ligands against the elusive transient, primary reactions that often lead to protein misfolding. This development will provide a highly desirable tool for the pharmaceutical, academic, and medical professions.
Naik
Subhashchandra
S
Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS, USA.
Haque
Inamul
I
Degner
Nick
N
Kornilayev
Boris
B
Bomhoff
Gregory
G
Hodges
Jacob
J
Khorassani
Ara-Azad
AA
Katayama
Hiroo
H
Morris
Jill
J
Kelly
Jeffery
J
Seed
John
J
Fisher
Mark T
MT
D018834:Chaperonin 60 / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D008024:Ligands; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D013816:Thermodynamics; D013884:Thiosulfate Sulfurtransferase / Q000737:chemistry / Q000378:metabolism; D014462:Ultrafiltration / Q000379:methods; D001613:beta 2-Microglobulin / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism
D018834:Chaperonin 60; D008024:Ligands; D018832:Molecular Chaperones; D001613:beta 2-Microglobulin; D013884:Thiosulfate Sulfurtransferase