Factors responsible for the persistent adoption of hairpin conformations by hybrid oligopeptides, each having a central β/α dipeptide segment flanked by aromatic γ-amino acid (γAr) residues, are probed. Our recent studies revealed that tetrapeptide 1 and 2, having central dipeptide segments consisting of β-alanine (β-Ala) and glycine (Gly), and L-β-homophenylalanine (L-β-homoPhe) and Gly residues, respectively, that are flanked by γAr residues, fold into well-defined, expanded β-turns with doubly H-bonded γAr residues. Replacing the γAr residues of 1 and 2 with L-Val and L-Leu residues results in tetrapetides 1′ and 2′ that fail to fold into defined conformations, which confirms the decisive role played by the H-bonded γAr residues in the promoting folding of 1 and 2. Attaching L-Val and L-Leu residues to the termini of 1 affords hexapeptide 1a. With an additional H-bond between its L-Val and L-Leu residues, peptide 1a folds into a hairpin with higher stability than that of 1, indicating that the expanded β-turn can nucleate and stabilize β-hairpin with longer β-strands. Attaching L-Val and L-Leu residues to the termini of 2 affords hexapeptide 2a. Substituting the L-β-homoPhe residue of 2a with a D-β-homoPhe residue gives hexapeptide 2b. Surprisingly, hexapeptide 2a fold into a hairpin showing the similar stability as those of tetrapeptides 1 and 2. Hexapeptide 2b, with its combination of a D-β-homoPhe residue and the L-Val/L-Leu pair, fold into a hairpin that is significantly more stable than the other hybrid peptides, demonstrating that a combination of hetero-chirality between the β-amino acid residue of the dipeptide loop and the α-amino acid residues of the β-strands enhances the stability of the resultant β-hairpin.

探究了混合寡肽持续采用发夹构象的因素，每个混合寡肽都有一个中央 β/α 二肽片段，两侧是芳香族 γ-氨基酸 (γAr) 残基。我们最近的研究表明，四肽1和2，具有分别由 β-丙氨酸 (β-Ala) 和甘氨酸 (Gly) 以及 L-β-高苯丙氨酸 (L-β-homoPhe) 和甘氨酸残基组成的中心二肽片段，两侧是 γAr 残基，折叠成孔-定义的、扩展的β-转角，具有双氢键合的γAr残基。取代 γAr 残基1和2具有 L-Val 和 L-Leu 残基会产生四肽1′和2′未能折叠成确定的构象，这证实了H键合的γAr残基在促进折叠中发挥的决定性作用1和2。将 L-Val 和 L-Leu 残基连接到1提供六肽1a。L-Val 和 L-Leu 残基之间有一个额外的氢键，肽1a折叠成发夹状，稳定性比1，表明扩展的β-转角可以成核并稳定具有较长β-链的β-发夹。将 L-Val 和 L-Leu 残基连接到2提供六肽2a。取代 L-β-homoPhe 残基2a带有 D-β-homoPhe 残基得到六肽2b。令人惊讶的是，六肽2a折叠成发夹，显示出与四肽相似的稳定性1和2。六肽2b其由 D-β-同型苯丙氨酸残基和 L-Val/L-Leu 对组合而成，折叠成比其他杂合肽更稳定的发夹结构，表明 β- 之间的异手性组合二肽环的氨基酸残基和β-链的α-氨基酸残基增强了所得β-发夹的稳定性。