Opening book details…
Can I read Pharmacological Stabilization of the Native State of Full-length Immunoglobulin Light Chains to Treat Light Chain Amyloidosis on EtoBox?
Pharmacological Stabilization of the Native State of Full-length Immunoglobulin Light Chains to Treat Light Chain Amyloidosis by Nicholas L. Yan; Gareth J. Morgan; H. Michael Petrassi; Ian A. Wilson; Jeffery W. Kelly is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.
What is Pharmacological Stabilization of the Native State of Full-length Immunoglobulin Light Chains to Treat Light Chain Amyloidosis about?
Immunoglobulin light chain amyloidosis (AL) is a cancer of plasma cells that secrete unstable full-length immunoglobulin light chains. These light chains misfold and aggregate, often with aberrant endoproteolysis, leading to organ toxicity. AL is currently treated by pharmacological elimination of the clonal plasma cells. Since it remains difficult to completely kill these cells in the majority of patients, we seek a complementary drug that inhibits light chain aggregation, which should diminish organ toxicity. We discovered a small-molecule binding site on full-length immunoglobulin light chains by structurally characterizing hit stabilizers emerging from a high-throughput screen seeking small molecules that protect full-length light chains from conformational excursion-linked endoproteolysis. The x-ray crystallographic characterization of 7 structurally distinct hit native-state stabilizers provided a structure-based blueprint, reviewed herein, to design more potent stabilizers. This approach enabled us to transform hits with micromolar affinity into stabilizers with nanomolar dissociation constants that potently prevent light chain aggregation.
Who reads Pharmacological Stabilization of the Native State of Full-length Immunoglobulin Light Chains to Treat Light Chain Amyloidosis?
It is typically read by researchers, students, and practitioners in Biochemistry, Genetics and Molecular Biology.
- Author
- Nicholas L. Yan; Gareth J. Morgan; H. Michael Petrassi; Ian A. Wilson; Jeffery W. Kelly
- Publisher
- Elsevier BV
- Published
- 2023
- Language
- EN
- Field
- Biochemistry, Genetics and Molecular Biology (Life Sciences)