Fig. 4. Representative graphs of the most effective peptidomimetics on the cyclic adenosine monophosphate (cAMP) production induced by the full agonist isoproterenol (ISO) at the β₂-adrenergic receptor (β₂AR). The stapled peptidomimetic 10C inhibited the maximal response of ISO to 61% whereas its linear precursor 6C had no significant effect on the ISO-induced cAMP production (A). The linear 7B (B) and stapled peptidomimetic 11C (C) inhibited ISO efficacy to a smaller degree (∼80%) but significantly. Their stapled (11B) and linear counterparts (7C) had a minor (∼90%) albeit non-statistically significant effects. The linear 8B and stapled peptidomimetic 12B pair decreased the maximum response of ISO to 70–80% (D), which is also the case for the linear and stapled pair 8C and 12C (E). The linear 9B and stapled peptidomimetic 13B, decreased the potency of ISO by 39- and 8-fold, respectively, whereas the efficacy was not affected (F). In presence of ISO corresponding to EC₇₅, the IC₅₀ of 10C was estimated to 55 μM, and the IC₅₀ of Nb80 was estimated to 0.40 μM (G).