Abstract: | Two sterically constrained peptides {iBoc-Aib-Aib-Aib-DkNap-Leu-Qx-Ala-Aib-Aib-F1, (Dk4Qx6[7/9]) 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/p[7/9] and Dk4Qx6[7/9] 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. |