Formaggio F, Pegoraro S, Crisma M, Valle G, Toniolo C, Précigoux G, Boesten W H, Schoemaker H E, Kamphuis J
C.N.R., Department of Organic Chemistry, University of Padova, Italy.
J Biomol Struct Dyn. 1993 Apr;10(5):919-31. doi: 10.1080/07391102.1993.10508684.
The crystal-state preferred conformations of two tripeptides, one tetrapeptide, and one pentapeptide, each containing a single residue of the chiral, C alpha, alpha-disubstituted glycine C alpha-methyl, C alpha-benzylglycine [(alpha Me)Phe], have been determined by X-ray diffraction. The tripeptides are Z-L-(alpha Me)Phe-(Aib)2-OH dihydrate and Z-Aib-D-(alpha Me)Phe-Aib-OtBu, the tetrapeptide is Z-(Aib)2-D-(alpha Me)Phe-Aib-OtBu, and the pentapeptide is pBrBz-(Aib)2-DL-(alpha Me)Phe-(Aib)2-OtBu. While the two tripeptides are folded in a beta-bend conformation, two such conformations are consecutively formed by the tetrapeptide. The pentapeptide adopts a regular 3(10)-helix promoted by three consecutive beta-bends. This study confirms the strong propensity of short peptides containing C alpha-methylated alpha-aminoacids to fold into beta-bends and 3(10)-helical structures. Since Aib is achiral, the handedness of the observed bends and helices is dictated by the presence of the (alpha Me)Phe residue. In general, we have found that the relationship between (alpha Me)Phe chirality and helix handedness is opposite to that exhibited by protein aminoacids. A comparison with the preferred conformation of other extensively investigated C alpha-methylated aminoacids is made.
通过X射线衍射确定了两种三肽、一种四肽和一种五肽的晶体态优选构象，每种肽均含有一个手性Cα，α-二取代甘氨酸残基，即Cα-甲基、Cα-苄基甘氨酸[（αMe）Phe]。三肽分别为Z-L-（αMe）Phe-（Aib）2-OH二水合物和Z-Aib-D-（αMe）Phe-Aib-OtBu，四肽为Z-（Aib）2-D-（αMe）Phe-Aib-OtBu，五肽为pBrBz-（Aib）2-DL-（αMe）Phe-（Aib）2-OtBu。虽然这两种三肽折叠成β-转角构象，但四肽连续形成了两种这样的构象。五肽通过三个连续的β-转角形成规则的3（10）-螺旋。这项研究证实了含有Cα-甲基化α-氨基酸的短肽强烈倾向于折叠成β-转角和3（10）-螺旋结构。由于Aib是非手性的，观察到的转角和螺旋的手性由（αMe）Phe残基的存在决定。一般来说，我们发现（αMe）Phe手性与螺旋手性之间的关系与蛋白质氨基酸所表现出的关系相反。还与其他广泛研究的Cα-甲基化氨基酸的优选构象进行了比较。
