Department of Chemistry, Slippery Rock University , Slippery Rock, Pennsylvania 16057, United States.
Department of Chemistry, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
Org Lett. 2016 Aug 5;18(15):3902-5. doi: 10.1021/acs.orglett.6b01936. Epub 2016 Jul 20.
Peptides containing α,α-dialkylated α-amino acids, owing to their ability to disrupt aggregation of β-amyloid proteins, have therapeutic potential in the treatment of neurodegenerative diseases. Thermodynamic and structural analyses are reported for a series of β-hairpin peptides containing α,α-dialkylated α-amino acids with varying side-chain lengths. The results of these experiments show that α,α-dialkylated α-amino acids with side-chain lengths longer than one carbon unit are tolerated in a β-hairpin, although at a moderate cost to folded stability.
含有α,α-二取代α-氨基酸的肽，由于其能够破坏β-淀粉样蛋白的聚集，因此在治疗神经退行性疾病方面具有治疗潜力。本文报道了一系列含有α,α-二取代α-氨基酸的β-发夹肽的热力学和结构分析，这些氨基酸的侧链长度不同。这些实验的结果表明，在β-发夹中可以容忍具有一个以上碳原子长度的α,α-二取代α-氨基酸，尽管这会对折叠稳定性造成适度的损失。
