Aggregation of Full-length Immunoglobulin Light Chains from Systemic Light Chain Amyloidosis (AL) Patients Is Remodeled by Epigallocatechin-3-gallate.

Intervention into amyloid deposition with anti-amyloid agents like the polyphenol epigallocatechin-3-gallate (EGCG) is emerging as an experimental secondary treatment strategy in systemic light chain amyloidosis (AL). In both AL and multiple myeloma (MM), soluble immunoglobulin light chains (LC) are produced by clonal plasma cells, but only in AL do they form amyloid deposits We investigated the amyloid formation of patient-derived LC and their susceptibility to EGCG to probe commonalities and systematic differences in their assembly mechanisms. We isolated nine LC from the urine of AL and MM patients.

The Effect of (-)-Epigallo-catechin-(3)-gallate on Amyloidogenic Proteins Suggests a Common Mechanism.

Studies on the interaction of the green tea polyphenol (-)-Epigallocatechin-3-gallate (EGCG) with fourteen disease-related amyloid polypeptides and prions Huntingtin, Amyloid-beta, alpha-Synuclein, islet amyloid polypeptide (IAPP), Sup35, NM25 and NM4, tau, MSP2, semen-derived enhancer of virus infection (SEVI), immunoglobulin light chains, beta-microglobulin, prion protein (PrP) and Insulin, have yielded a variety of experimental observations. Here, we analyze whether these observations could be explained by a common mechanism and give a broad overview of the published experimental data on the actions of EGCG. Firstly, we look at the influence of EGCG on aggregate toxicity, morphology, seeding competence, stability and conformational changes.

Dasatinib, imatinib and staurosporine capture compounds - Complementary tools for the profiling of kinases by Capture Compound Mass Spectrometry (CCMS).

Capture Compound Mass Spectrometry (CCMS) is a platform technology for the functional isolation of subproteomes. Here we report the synthesis of two new kinase Capture Compounds (CCs) based on the tyrosine-kinase specific inhibitors dasatinib and imatinib and compare their interaction profiles to that of our previously reported staurosporine-CCs. CCs are tri-functional molecules: they comprise a sorting function (e.

Comprehensive identification of staurosporine-binding kinases in the hepatocyte cell line HepG2 using Capture Compound Mass Spectrometry (CCMS).

The central role of kinases in cell signaling has set them in the focus of biomedical research. In functional proteomics analyses, large- scale profiling of kinases has become feasible through the use of affinity pulldown beads that carry immobilized kinase inhibitors. As an alternative approach to solid phase beads, Capture Compound Mass Spectrometry (CCMS) enables the functional isolation of protein-classes on the basis of small molecule-protein interactions in solution.