The α_Vβ₃-receptor, one member of the integrin family, is implicated in angiogenesis and in human tumor metastasis. Spatial screening led to the highly active first-generation peptide c(RGDfV), which shows a βII‘/γ-turn arrangement with d-Phe in the i + 1 position of the βII‘-turn. Further reduction of the flexibility should be achieved by incorporating different rigid building blocks (turn mimetics) like the (S)- and (R)-Gly[ANC-2]Leu dipeptide, the β-turn dipeptide (BTD) and the (S,S)-spiro-Pro-Leu moiety. These distinct β-turn mimetics are introduced by replacing the d-Phe-Val dipeptide in the lead structure c(RGDfV). In peptide analogues c(RGD“S-ANC”) (PA1), c(RGD“R-ANC”) (PA2), and c(RGD“BTD”) (PA3) the turn mimetic does not adopt the desired position in the β-turn, instead Gly occupies the i + 1 position of the βII‘-turn. Only c(RGD“spiro”) PA4 led to the desired βII‘/γ-turn arrangement with the turn motif in the i + 1 and i + 2 position of the β-turn. These effects may arise from particular steric effects of the cyclic pentapeptide system in combination with steric requirements of the ANC and BTD moiety. Additional investigations on cyclic hexapeptide derivatives show that the BTD occupies the expected i + 1 and i + 2 position of a βII‘-turn in these systems. Structure−activity investigations showed that the incorporation of the rigid turn motifs could not reduce the flexibility of the RGD site (ANC and BTD) or fix a conformation which is unable to match the receptor very well (spiro). On the other hand, recent findings that the proton of the amide bond between Asp and the following amino acid is essential for high activity can be confirmed. Moreover, the synthesis of c(RGD“R-ANC”) PA2 led to one of the compounds most active in inhibiting vitronectin binding to the α_Vβ₃-integrin.