title: Inhibition of Light Chain 6aJL2-R24G Amyloid Fiber Formation Associated with Light Chain Amyloidosis.
abstract: Light chain amyloidosis (AL) is a deadly disease characterized by the deposition of monoclonal immunoglobulin light chains as insoluble amyloid fibrils in different organs and tissues. Germ line λ VI has been closely related to this condition; moreover, the R24G mutation is present in 25% of the proteins of this germ line in AL patients. In this work, five small molecules were tested as inhibitors of the formation of amyloid fibrils from the 6aJL2-R24G protein. We have found by thioflavin T fluorescence and transmission electron microscopy that EGCG inhibits 6aJL2-R24G fibrillogenesis. Furthermore, using nuclear magnetic resonance spectroscopy, dynamic light scattering, and isothermal titration calorimetry, we have determined that the inhibition is due to binding to the protein in its native state, interacting mainly with aromatic residues.
authors.affiliation: †Laboratorio de Bioquímica y Resonancia Magnética Nuclear, Centro de Investigaciones Químicas, Instituto de Investigación en Ciencias Básicas y Aplicadas, Universidad Autónoma del Estado de Morelos, Cuernavaca, México.
authors.forename: Angel E
authors.initials: AE
authors.lastname: Pelaez-Aguilar
authors.affiliation: †Laboratorio de Bioquímica y Resonancia Magnética Nuclear, Centro de Investigaciones Químicas, Instituto de Investigación en Ciencias Básicas y Aplicadas, Universidad Autónoma del Estado de Morelos, Cuernavaca, México.
authors.forename: Lina
authors.initials: L
authors.lastname: Rivillas-Acevedo
authors.affiliation: †Laboratorio de Bioquímica y Resonancia Magnética Nuclear, Centro de Investigaciones Químicas, Instituto de Investigación en Ciencias Básicas y Aplicadas, Universidad Autónoma del Estado de Morelos, Cuernavaca, México.
authors.forename: Leidys
authors.initials: L
authors.lastname: French-Pacheco
authors.affiliation: ‡Centro de Investigación en Dinámica Celular, Instituto de Investigación en Ciencias Básicas y Aplicadas, Universidad Autónoma del Estado de Morelos, Cuernavaca, México.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Valdes-Garcia
authors.affiliation: †Laboratorio de Bioquímica y Resonancia Magnética Nuclear, Centro de Investigaciones Químicas, Instituto de Investigación en Ciencias Básicas y Aplicadas, Universidad Autónoma del Estado de Morelos, Cuernavaca, México.
authors.forename: Roberto
authors.initials: R
authors.lastname: Maya-Martinez
authors.affiliation: ‡Centro de Investigación en Dinámica Celular, Instituto de Investigación en Ciencias Básicas y Aplicadas, Universidad Autónoma del Estado de Morelos, Cuernavaca, México.
authors.forename: Nina
authors.initials: N
authors.lastname: Pastor
authors.affiliation: †Laboratorio de Bioquímica y Resonancia Magnética Nuclear, Centro de Investigaciones Químicas, Instituto de Investigación en Ciencias Básicas y Aplicadas, Universidad Autónoma del Estado de Morelos, Cuernavaca, México.
authors.forename: Carlos
authors.initials: C
authors.lastname: Amero
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000682:Amyloid / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics*; D000686:Amyloidosis / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics*; D066298:In Vitro Techniques; D008550:Melatonin / Q000494:pharmacology; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding / Q000187:drug effects; D055503:Protein Multimerization / Q000187:drug effects; D011794:Quercetin / Q000494:pharmacology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D012293:Rifampin / Q000494:pharmacology; D013752:Tetracycline / Q000494:pharmacology
chemical_list: D000682:Amyloid; D007147:Immunoglobulin Light Chains; D011994:Recombinant Proteins; D002392:Catechin; D011794:Quercetin; C045651:epigallocatechin gallate; D013752:Tetracycline; D008550:Melatonin; D012293:Rifampin