In some cases, helical peptides stabilized by an i, i + 7 tether exhibit bettertargetbindingandcellularfunctionscomparedtotheiri, i+4 analogues. Herein, we carried out a systematic study of the eﬀects of an in-tether chiral center on the i, i + 7 system. We screened the optimal cross linking mode, tether length, in-tether chiral center positions, and absolute configurations. From these studies, we determined that a chiral center of R absolute configuration at the c-position totheC-terminalofa10-memberedtethercouldfunctiontoeﬃciently induce helicity of the backbone peptides. This is an important addition to the current i, i + 4 in-tether chiral center induced helicity strategy (CIH strategy), and could have broad biological applications.