PROTEIN CHEMISTRY CORE

University Of California Los Angeles, Los Angeles CA

Investigators

Linked publications & trials

Abstract

The "Pathologic Protein Folding and Human Disease" program project application (Program)[unreadable] proposes experimental and computational studies of protein folding and assembly. These studies[unreadable] have relevance to Alzheimer's disease (AD) and other diseases in which pathologic protein folding[unreadable] and aggregation are involved, including Parkinson's, Huntington's, and prion disease. The Peptide[unreadable] Chemistry Core (Core B) will provide chemical synthesis and analysis services to projects 1, 2, 3,[unreadable] and 5. The starting point for the majority of the experimental studies is the amyloid beta-protein (Abeta),[unreadable] which exists in vivo predominately as a 40-42 residue peptide. Core B will synthesize and[unreadable] characterize wild type Abeta peptides and a variety of structurally-related full-length analogues and[unreadable] peptide fragments. Syntheses will be done primarily using automated solid-phase peptide[unreadable] synthesis (SPPS) and FMOC chemistry. Peptide purification will be done using preparative reverse[unreadable] phase HPLC. To characterize the synthetic products, a combination of quantitative amino acid[unreadable] analysis, analytical HPLC, protein sequencing, and mass spectrometry will be used. In addition to[unreadable] direct provision of starting materials and expertise to projects 1, 2, 3, and 5, Core B will synthesize[unreadable] Abeta peptides in which structural modifications will be made to test hypotheses emerging from project[unreadable] 4. Project 4 will utilize in silico approaches to simulate Abeta folding and assembly. These peptides[unreadable] will be provided to the other projects, as appropriate, to perform actual, as opposed to "virtual,"[unreadable] experiments.[unreadable] Dr. Teplow (Director) has been involved in the development and application of methods for peptide[unreadable] and protein synthesis, analysis, and study for almost 25 years (1-55). Ms. Condron (Senior[unreadable] Research Associate) is equally experienced in peptide chemistry and instrumentation and has been[unreadable] working with Dr. Teplow for almost 15 years. In addition to the strictly technical contributions of[unreadable] Core B to the Program, Dr. Teplow, Ms. Condron, and other Core B personnel will collaborate with[unreadable] each of the five projects in the design of physical and virtual peptides for hypothesis testing and to[unreadable] address any technical problems that emerge during the execution of the aims of the projects.