Peptide flexibility is a determining factor in designing peptide-based drugs and in linker peptides. The flexibility is roughly inversely proportional to the size of the amino acid side chains in a peptide sequence. Glycine homo repeats are, therefore, the most flexible oligopeptides. We synthesized three oligopeptides: a relatively rigid peptide, His-(Arg)₄-Trp (1), a flexible peptide, His-(Gly)₄-Trp (2), and a “super-flexible” peptide; His-Gly-(GABA)-Gly-Trp (3) in which the central Gly-Gly unit in 2 was substituted by a γ-aminobutyric acid (GABA) linker. The only structural difference between 2 and 3 is that an amide bond in 2 is replaced by –CH₂– units in 3. The frequency of end-to-end collisions, which serves as indicator of peptide flexibility, was measured fluorometrically. For comparing peptide flexibility, fluorescence emission spectra of their tryptophan residues were compared. Upon end-to-end collision, the N-terminal histidine residue efficiently quenches the fluorescence emission of the C-terminal tryptophan residue. The quenching rate is directly proportional to the peptide flexibility. The observed strongly increased flexibility in the γ-aminobutyric acid-containing peptide is due to the substitution of a single, rotationally restricted amide bond. Our result demonstrates the importance of amid bonds in limiting peptide dynamics.

肽的柔韧性是设计基于肽的药物和接头肽的决定因素。柔韧性与肽序列中氨基酸侧链的大小大致成反比。因此，甘氨酸同源重复序列是最灵活的寡肽。我们合成了三种寡肽：相对刚性的肽His-（Arg）₄ -Trp（1），柔性肽，His-（Gly）₄ -Trp（2）和“超柔性”肽；他的-Gly-（GABA）-Gly-色氨酸（3），其中在中央甘氨酸-甘氨酸单元2是由γ氨基丁酸（GABA）的接头取代。2和3之间的唯一结构差异是，在酰胺键2是由-CH代替₂ -在单元3。用荧光法测量了端到端碰撞的频率，该频率可作为肽柔韧性的指标。为了比较肽的柔韧性，比较了其色氨酸残基的荧光发射光谱。端到端碰撞后，N端组氨酸残基有效地淬灭了C端色氨酸残基的荧光发射。淬灭速率与肽的柔韧性成正比。在含γ-氨基丁酸的肽中观察到的柔韧性大大提高是由于单个旋转受限的酰胺键的取代。我们的结果证明了酰胺键在限制肽动力学中的重要性。