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.
Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS, USA.
Subhashchandra
S
Naik
Inamul
I
Haque
Nick
N
Degner
Boris
B
Kornilayev
Gregory
G
Bomhoff
Jacob
J
Hodges
Ara-Azad
AA
Khorassani
Hiroo
H
Katayama
Jill
J
Morris
Jeffery
J
Kelly
John
J
Seed
Mark T
MT
Fisher
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