Kirshenbaum K, Barron A E, Goldsmith R A, Armand P, Bradley E K, Truong K T, Dill K A, Cohen F E, Zuckermann R N
Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143.
Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4303-8. doi: 10.1073/pnas.95.8.4303.
We have synthesized and characterized a family of structured oligo-N-substituted-glycines (peptoids) up to 36 residues in length by using an efficient solid-phase protocol to incorporate chemically diverse side chains in a sequence-specific fashion. We investigated polypeptoids containing side chains with a chiral center adjacent to the main chain nitrogen. Some of these sequences have stable secondary structure, despite the achirality of the polymer backbone and its lack of hydrogen bond donors. In both aqueous and organic solvents, peptoid oligomers as short as five residues give rise to CD spectra that strongly resemble those of peptide alpha-helices. Differential scanning calorimetry and CD measurements show that polypeptoid secondary structure is highly stable and that unfolding is reversible and cooperative. Thermodynamic parameters obtained for unfolding are similar to those obtained for the alpha-helix to coil transitions of peptides. This class of biomimetic polymers may enable the design of self-assembling macromolecules with novel structures and functions.
我们通过使用一种高效的固相方法，以序列特异性方式掺入化学性质多样的侧链，合成并表征了一系列长度达36个残基的结构化寡聚N-取代甘氨酸（类肽）。我们研究了主链氮原子相邻带有手性中心侧链的类肽。尽管聚合物主链是非手性的且缺乏氢键供体，但其中一些序列具有稳定的二级结构。在水性和有机溶剂中，短至五个残基的类肽低聚物产生的圆二色光谱与肽α-螺旋的光谱非常相似。差示扫描量热法和圆二色测量表明，类肽二级结构高度稳定，且解折叠是可逆且协同的。解折叠获得的热力学参数与肽α-螺旋至无规卷曲转变获得的参数相似。这类仿生聚合物可能有助于设计具有新颖结构和功能的自组装大分子。
