Ahmed Sahar, Sprules Tara, Kaur Kamaljit
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada, T6G 2E1; Department of Pharmacognosy and Medicinal Chemistry, Faculty of Pharmacy, Taibah University, Al-Madinah Al-munawarah, 41477, Kingdom of Saudi Arabia.
Biopolymers. 2014 Jul;102(4):359-67. doi: 10.1002/bip.22510.
Formation of stable secondary structures by oligomers that mimic natural peptides is a key asset for enhanced biological response. Here we show that oligomeric β(3)-hexapeptides synthesized from L-aspartic acid monomers (β(3)-peptides 1, 5a, and 6) or homologated β(3)-amino acids (β(3)-peptide 2), fold into similar stable 14-helical secondary structures in solution, except that the former form right-handed 14-helix and the later form left-handed 14-helix. β(3)-Peptides from L-Asp monomers contain an additional amide bond in the side chains that provides opportunities for more hydrogen bonding. However, based on the NMR solution structures, we found that β(3)-peptide from L-Asp monomers (1) and from homologated amino acids (2) form similar structures with no additional side-chain interactions. These results suggest that the β(3)-peptides derived from L-Asp are promising peptide-mimetics that can be readily synthesized using L-Asp monomers as well as the right-handed 14-helical conformation of these β(3)-peptides (such as 1 and 6) may prove beneficial in the design of mimics for right-handed α-helix of α-peptides.
由模拟天然肽的寡聚体形成稳定的二级结构是增强生物反应的关键特性。在此我们表明，由L-天冬氨酸单体（β(3)-肽1、5a和6）或同系β(3)-氨基酸（β(3)-肽2）合成的寡聚β(3)-六肽在溶液中折叠成相似的稳定14-螺旋二级结构，只是前者形成右手14-螺旋，后者形成左手14-螺旋。来自L-天冬氨酸单体的β(3)-肽在侧链中含有一个额外的酰胺键，这为更多氢键的形成提供了机会。然而，基于核磁共振溶液结构，我们发现来自L-天冬氨酸单体（1）和同系氨基酸（2）的β(3)-肽形成相似的结构，没有额外的侧链相互作用。这些结果表明，源自L-天冬氨酸的β(3)-肽是有前景的肽模拟物，它们可以很容易地用L-天冬氨酸单体合成，并且这些β(3)-肽（如1和6）的右手14-螺旋构象在设计α-肽右手α-螺旋模拟物时可能被证明是有益的。
