Scientific Reports: Peptide Targeting PI3Kγ A-Kinase Anchoring Function Shows Inhaled Delivery Properties for Pulmonary cAMP Modulation
A 2026 Scientific Reports paper characterized the biophysical and aerodynamic properties of PI3Kγ MP (KIT2014), a non-natural peptide that disrupts the AKAP-PKA interaction by mimicking PI3Kγ's A-kinase anchoring function. The peptide adopts a partially structured conformation essential for PKA binding, assembles into dynamic nanoparticles compatible with epithelial and mucus penetration, and retains full biological activity in protease-rich environments — enhancing β₂-adrenergic receptor-driven cAMP signaling to promote airway relaxation, mucus clearance, and reduced inflammation in pulmonary cells. The work builds the case for peptide-based AKAP disruptors as inhaled therapeutics for chronic inflammatory airway diseases including asthma and COPD.