Optimization of a TREM2 receptor inhibitor peptide

Triggering receptor expressed on myeloid cells 2 (TREM2) is an immune receptor regulating the inflammatory response and involved in neurodegenerative, chronic and autoimmune diseases. TREM2 is an orphan receptor, and the research of new ligands has recently become a hot topic. In this context, the peptide sequence IA9 (H-IFLIKILAA-OH) has been rationally designed for inhibition of TREM2 [1]. In order to deeper analyze the mechanism of interaction with TREM2 and select molecules with specific binding, we synthetized a series of IA9 peptide analogues where the Lys residues was replaced by either Gly or Ala to explore the effect of the residue side chain charge and polarity in this position that is believed to be fundamental for ligand interaction. Their conformation, their ability to interact with membranes, and their biological activity was investigated