Cyclization of several linear penta‐ and heptapeptides with different metal ions studied by CD spectroscopy*

Abstract: A cyclic pentapeptide c(Tyr‐Leu‐Ala‐Gly‐Pro) ( I ), which was isolated and identified from Pseudostellaria heterophylla medicinal herbs, and two cyclic heptapeptides, c(Gly‐Tyr‐Gly‐Gly‐Pro‐Phe‐Pro) ( II ) and c(Gly‐Ile‐Pro‐Tyr‐Ile‐Ala‐Ala) ( III ), which were isolated and identified from Stellaria yunnanensis Franch (M), were synthesized by using 3‐(diethoxyphosphoryloxy)‐1,2,3‐benzotriazin‐4(3 H)‐one (DEPBT) as a coupling reagent in solution, and mediated by different metal ions, from their linear peptide precursors H‐Tyr‐Leu‐Ala‐Gly‐Pro‐OH ( I‐1 ) and H‐Ala‐Gly‐Pro‐Tyr‐Leu‐OH ( I‐2 ), H‐Gly‐Tyr‐Gly‐Gly‐Pro‐Phe‐Pro‐OH ( II‐1 ) and H‐Gly‐Ile‐Pro‐Tyr‐Ile‐Ala‐Ala‐OH ( III‐1 ), respectively. The results show that alkali metal ions can improve the cyclization yields and/or the cyclization rates of linear peptide precursors, such as Na⁺ ion is favorable for the cyclization of linear pentapeptides and Cs⁺ ion is favorable for the cyclization of linear heptapeptides, while some bivalent and trivalent metal ions, such as Mg²⁺, Ca²⁺, Zn²⁺, Fe²⁺, Ni²⁺ and Cr³⁺ reduced/inhibited both the cyclization yields and the cyclization rates of the linear peptide precursors. The circular dichroism spectra of I‐1 , II‐1 and III‐1 with different metal ions were studied to elucidate the changes in their secondary structures. It is shown that Cs⁺ can induce and stabilize the type I β‐turn conformation in the linear heptapeptide II‐1 and the type II β‐turn conformation in the linear heptapeptide III‐1 .