The role exercised by the central residue of the chemotactic N-formyltripeptide HCO-Met-Leu-Phe-OMe (fMLP-OMe) in controlling both the backbone conformation and the biochemical activity is the subject of recent interest. Here, two new centrally constrained fMLP-OMe analogues, namely HCO-Met-azaPro-Phe-OMe (4) and HCO-Met-(γ-lactam)-Phe-OMe (6) have been synthesized and their CDCl3 solution conformation and activity have been studied. The azapeptide 4 adopts β-folded conformation with the azaPro residue at the i+2 position and an intramolecular H-bond involving the formylic oxygen and the Phe NH. The γ-lactam tripeptide 6 prefers a semi-extended backbone conformation. When tested on human neutrophils both the new models were found practically devoid of biological activity. The role exerted by the NH groups as well as by the conformational preferences is discussed.