DID YOU KNOW? DTIC has over 3.5 million final reports on DoD funded research, development, test, and evaluation activities available to our registered users. Click
HERE to register or log in.
Accession Number:
AD1016194
Title:
Inhibitors of SOD1 Interaction as an Approach to Slow the Progressive Spread of ALS Symptoms
Corporate Author:
University of Florida Gainsville United States
Report Date:
2016-07-01
Abstract:
Our goal is to discover drugs that stabilize the normal structure of superoxide dismutase 1 as a means to slow the progression of ALS caused by mutations in this protein. To accomplish this goal, we developed an assay that is based on the observation that the luciferase enzyme can be split into 2 halves. These 2 halves can be forced to reconstitute an active enzyme if they are brought together by some force. In our assay, this force is the normal interaction that occurs when 2 individual SOD1 proteins come together to form a normal active enzyme. Using recombinant DNA, we create fusion proteins of SOD1 and each half of the luciferase enzyme. In the past year, we have characterized and optimized an assay that measures the strength of interaction between SOD1 proteins by measuring luciferase activity. We have demonstrated that the assay reports the stability of normal dimeric interactions, and interactions between normal and disease-associated mutant SOD1. Information obtained during the screen helped us identify a candidate compound that may stabilize SOD1 dimer interactions. We have also used the assay to perform an initial screen of a drug library.
Descriptive Note:
Technical Report,01 Jul 2015,30 Jun 2016
Pages:
0040
Distribution Statement:
Approved For Public Release;
File Size:
0.98MB
