Design and Synthesis of Peptide Modulators of Gαi/s Proteins

Our studies with different combinatorial peptide libraries revealed novel Gi/s modulators with distinct guanine nucleotide exchange activities.Compounds GPM-2, GPM-3, and peptide 10 were identified from an OBTC peptide library with promising selectivity for Gi.In silico studies unveiled new important structural features for Gi binding, which were confirmed by comparison of peptide 10 to the Gi modulators GPM-2 and GPM-3.These findings provide fundamental knowledge for deeper investigations of peptide 10, and optimization of the biological properties of the obtained compounds to achieve higher pharmacological potencies.