Conformational preferences of oligopeptides rich in α-aminoisobutyric acid. III. Design,synthesis and hydrogen bonding in 310-helices

Two sterically constrained peptides {ⁱBoc-Aib-Aib-Aib-DkNap-Leu-Qx-Ala-Aib-Aib-F1, (Dk⁴Qx⁶7/9]) and ⁱBoc-Aib-Aib-Aib-DkNap-Leu-Aib-Ala-Aib-Aib-Fl, (Dk⁴7/9)} containing α-aminoisobutyric acid (Aib) and Aib-class amino acids in conjunction with selected mono-α-alkyl amino acids were synthesized by an optimized TBTU/HOBt procedure. The use of Aib-class amino acids (e.g. DkNap and Qx), defined and discussed here, gives rise to the same overwhelmingly 3₁₀-helical backbone conformation as that provided by simpler Aib-rich peptides and homopeptides. The synthetic α,α-dialkylamino acids (DkNap, Qx) are aromatic homologues of the known alicyclic variants of Aib, the Ac₅c and Ac₆c amino acids. Two new organic solubilizing groups for peptides, ⁱBoc and 2-methoxyethylamine, are introduced. The ¹H nuclear magnetic resonance analyses of the Dk⁴s/p7/9] and Dk⁴Qx⁶7/9] peptides demonstrate the unambiguous 310s/b-helical hydrogen bonding pattern of these peptides, confirming the design objective of these sequence patterns containing greater than 50% Aib and Aib-class composition. © Munksgaard 1994.