Center for Molecular Biophysics & Biophysical Chemistry

Barbara Brodsky
Professor of Biochemistry, UMDNJ
(732) 235-4048
Robert Wood Johnson Medical School Tower, Room 609

My research focuses on the properties of the triple-helix protein motif, which is found in all collagens and in an important set of host-defense proteins. The triple-helix structure consists of three supercoiled polyproline II like chains, and requires the presence of Gly as every third residue and a high content of the imino acids proline and hydroxyproline. Triple-helical peptides are synthesized to model the basic features of the triple-helix, including their conformation, stability, folding and dynamics. A host-guest triple-helical peptide set was synthesized to evaluate the propensity of different Gly-X-Y triplets to adopt a triple-helical structure, and to characterize the interactions stabilizing this protein motif. In addition, peptides are designed to include important regions of collagen, or the macrophage scavenger receptor, to model binding regions and to study the structural alterations which occur in collagen diseases. Peptides studied thus far include an overlapping set of peptides which binds to a monoclonal antibody to type III collagen and a region adjacent to the unique collagenase cleavage sites.

The most well studied hereditary collagen disease is Osteogenesis Imperfecta, a disease characterized by fragile bones. Most of the cases are caused by a single point mutation which results in a substitution for a Gly residue along one of the chains of type I collagen. One set of peptides was designed to include 18 residues around a non-lethal Gly->Ser mutation site, and a second set of peptides included 18 residues around a lethal Gly-> Ser mutation site. It was observed that the Gly to Ser substitution caused a much greater decrease in triple-helix stability in the sequence around the lethal site, suggesting that the amino acid environment modulates the effect of Gly substitutions.