Gurunath R, Balaram P
Molecular Biophysics Unit, Indian Institute of Science, Bangalore.
Biochem Biophys Res Commun. 1994 Jul 15;202(1):241-5. doi: 10.1006/bbrc.1994.1918.
Non protein amino acids with strong secondary structure preferences are potentially useful in peptide design. alpha-Aminoisobutyric acid (Aib) is a powerful 'stereochemical director' of polypeptide chain folding, stabilizing helical conformations in diverse oligopeptide sequences. In an approach to the de novo design of alpha,alpha motifs, the 16 residue peptides Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-Xxx-Pro-Val-Ala-Leu-Aib-Val-Ala-Leu-OMe (Xxx = D-Phe 1; Xxx = L-Phe 2) have been spectroscopically studied in solution. Analysis of nuclear Overhauser effects, delineation of solvent shielded NH groups and circular dichroism spectra establish helical conformations in both the peptides. Despite the presence of a potentially helix breaking, central, (D)Phe-(L)Pro segment, peptide 1 is forced into a continuous helical fold presumably as a consequence of the overriding stereochemical dominance of the Aib residues.
具有强烈二级结构偏好的非蛋白质氨基酸在肽设计中可能很有用。α-氨基异丁酸（Aib）是多肽链折叠的强大“立体化学导向剂”，可稳定多种寡肽序列中的螺旋构象。在从头设计α,α基序的方法中，对16个残基的肽Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-Xxx-Pro-Val-Ala-Leu-Aib-Val-Ala-Leu-OMe（Xxx = D-Phe 1；Xxx = L-Phe 2）在溶液中进行了光谱研究。对核Overhauser效应的分析、溶剂屏蔽的NH基团的描绘以及圆二色光谱确定了两种肽中的螺旋构象。尽管存在潜在的螺旋破坏中心（D）Phe-（L）Pro片段，但肽1可能由于Aib残基占主导地位的立体化学作用而被迫形成连续的螺旋折叠。
