CONICET | Buscador de Institutos y Recursos Humanos

p { margin-bottom: 0.08in; direction: ltr; color: rgb(0, 0, 10); line-height: 120%; text-align: left; widows: 2; orphans: 2; }p.western { font-family: "Calibri",serif; }p.cjk { font-family: "Droid Sans Fallback"; }a:link { color: rgb(0, 0, 255); } Mitogen activated protein kinases (MAPKs) are serine/threonine kinases that play an important role in regulating various cellular processes including cell growth, differentiation, inflammation and apoptosis. The development of inhibitors of MAPKs is an important research area for various diseases such as cancer, diabetes, arthritis and inflammatory diseases. The kinase domain is highly abundant in the human genome, therefore it is very important to develop specific inhibitors for each particular MAPK. The first inhibitors used the ATP binding site as target (type I inhibitors) but this gave no specificity for each MAPK, the next generation compounds targeted a docking site right next to the ATP binding site (type II inhibitors) but these compounds do not inhibit MAPK activation. So the next leap was developing compounds that target the protein-protein docking site. Based on the crystal structure of p38α - MEF2A peptide complex, we calculated the binding energy of wild-type and point mutation peptides. We designed potential inhibitors with higher binding energy than the wt peptide.We selected 3 peptides, synthesized and tested them in activity experiments using radioactive ATP. Here, we present in vitro results of the inhibition effect of the selected peptides on the phosphorylation of ATF2, a transcription factor target of active p38α. Using this approach we found a potential inhibitor that not only has a slightlygreaterinhibitory effect than the wt peptide but also does not present the allosteric effect on ATP binding that wt has at low concentration,making it agood candidate for furthercharacterization.