Butcher D J, Bruch M D, Moe G R
Department of Chemistry and Biochemistry, University of Delaware, Newark 19716, USA.
Biopolymers. 1995 Aug;36(2):109-20. doi: 10.1002/bip.360360202.
CD and nmr spectroscopy were used to compare the conformational properties of two related peptides. One of the peptides, Model AB, was designed to adopt a helix-turn-extended strand (alpha beta) tertiary structure in water that might be stabilized by hydrophobic interactions between two leucine residues in the amino-terminal segment and two methionine residues in the carboxyl terminal segment. The other peptide, AB Helix, has the same amino acid sequence as Model AB except that it lacks the -Pro-Met-Thr-Met-Thr-Gly segment at the carboxyl-terminus. Although the carboxyl-terminal segment of Model AB was found to be unstructured, its presence increases the number of residues in a helical conformation, shifts the pKas of three ionizable side chains by 1 pH unit or more compared to an unstructured peptide, stabilizes the peptide as a monomer in high concentrations of ammonium sulfate, increases the conformational stability of residues at the terminal ends of the helix, and results in many slowly exchanging amide protons throughout the entire backbone of the peptide. These results suggest that interactions between adjacent segments in a small peptide can have significant structure organizing effects. Similar kinds of interactions may be important in determining the structure of early intermediates in protein folding and may be useful in the de novo design of independently folding peptides.
利用圆二色光谱（CD）和核磁共振光谱（NMR）比较了两种相关肽的构象性质。其中一种肽，即模型AB，设计为在水中采用螺旋-转角-延伸链（αβ）三级结构，这种结构可能通过氨基末端片段中的两个亮氨酸残基与羧基末端片段中的两个甲硫氨酸残基之间的疏水相互作用而得以稳定。另一种肽，AB螺旋，与模型AB具有相同的氨基酸序列，只是在羧基末端缺少-Pro-Met-Thr-Met-Thr-Gly片段。尽管发现模型AB的羧基末端片段是无结构的，但它的存在增加了处于螺旋构象的残基数量，与无结构肽相比，使三个可电离侧链的pKa值移动了1个pH单位或更多，在高浓度硫酸铵中使肽作为单体得以稳定，增加了螺旋末端残基的构象稳定性，并导致整个肽主链中有许多缓慢交换的酰胺质子。这些结果表明，小肽中相邻片段之间的相互作用可能具有显著的结构组织效应。类似的相互作用在确定蛋白质折叠早期中间体的结构中可能很重要，并且可能有助于独立折叠肽的从头设计。
