Abstract by Braden Kartchner
Chemistry and Biochemistry
Pam Van Ry
Design of Dimeric Galectin-1 as a Therapeutic for LGMD2B
Limb-girdle muscular dystrophy type 2B (LGMD2B) is a devastating autosomal recessive disease. It is characterized by gradual muscle atrophy in the proximal limb and pelvic regions, causing pain, social stigma, and chronic inflammation. The molecular basis for LGMD2B is a mutated form of the protein dysferlin. There are no current treatments that reverse or slow disease progression. We recently showed that recombinant human Galectin-1 (rHsGal-1) improves membrane repair in dysferlin-deficient myotubes and myofibers. Based on the crystal structure of Galectin-1, we hypothesize that rHsGal-1 dimerizes to form a lattice that helps myotubes fuse together. We designed a permanent linked dimeric form of rHsGal-1 (dGal-1) to test our hypothesis. We built a model of dGal-1 using Rosetta computational chemistry software and optimized the conformation to predict if energy levels would allow dGal-1 to relax into a stable state.