Peptide library approach to uncover phosphomimetic inhibitors of the BRCA1 C-terminal domain.

Many intracellular protein-protein interactions are mediated by the phosphorylation of serine, and phosphoserine-containing peptides can inhibit these interactions. However, hydrolysis of the phosphate by phosphatases, and the poor cell permeability associated with phosphorylated peptides has limited their utility in cellular and in vivo contexts. Compounding the problem, strategies to replace phosphoserine in peptide inhibitors with easily accessible mimetics (such as Glu or Asp) routinely fail.

Ion specific influences on the stability and unfolding transitions of a naturally aggregating protein; RecA.

The Escherichia coli RecA protein is a naturally aggregated protein complex that is affected by the presence of salts. In order to gain further insight into the nature of the ion-interactions on a naturally aggregating protein we used circular dichroism (CD), fluorescence and dynamic light scattering (DLS) to study the effects of different concentrations of MgCl2, CaCl2, NaCl, Na2SO4, and MgSO4 on RecA structure and thermal unfolding. The results show unique ion influences on RecA structure, aggregation, unfolding transitions and stability and the anion effects correlate with the reverse Hofmeister series.