Thursday,
November 20, 2008 - 4:00 P.M., NSH 184
Peptide Design Using Unnatural Amino Acids: Protein folding is dominantly governed by the separation of immiscible phases. By incorporating unnatural amino acids with fluorinated side chains into our peptide designs, we have introduced a phase into protein structure that is simultaneously hydrophobic and lipophobic (fluorocarbons form a separate phase from both hydrocarbons and water). Peptides with fluorinated surfaces can be programmed to self sort and aggregate only with other peptides that have fluorinated surfaces, and have enhanced thermodynamic structural stability. Furthermore, we established fluorinated surface driven peptide association in micellar lipid environments. This technology has implications in improving the stability of protein therapeutics.
Multivalent Antibody Aggregation: Immunoglobulins are multivalent agents of the immune system that bind and aggregate with antigens to generate immune responses. The smallest immunoglobulin unit is bivalent. In order to determine the enhancement gained through bivalency, we studied the thermodynamics and kinetics of the IgG binding process during aggregation that was stimulated using bivalent and trivalent hapten molecules. The equilibrium products of these interactions were generated in excess of ~90% yield upon mixing IgG and multivalent hapten molecules. The aggregates were more stable thermodynamically and kinetically than the interactions of this IgG with monomeric derivatives of its antigen; this stability suggests potential applications of these aggregates in biotechnology and antibody therapeutics.