Department of Chemistry and Biochemistry, Brigham Young University , Provo, Utah 84602, United States.
Org Lett. 2017 Oct 6;19(19):5190-5193. doi: 10.1021/acs.orglett.7b02455. Epub 2017 Sep 14.
The bulky dehydroamino acids dehydrovaline (ΔVal) and dehydroethylnorvaline (ΔEnv) can be inserted into the turn regions of β-hairpin peptides without altering their secondary structures. These residues increase proteolytic stability, with ΔVal at the (i + 1) position having the most substantial impact. Additionally, a bulky dehydroamino acid can be paired with a d-amino acid (i.e., d-Pro) to synergistically enhance resistance to proteolysis. A link between proteolytic stability and peptide structure is established by the finding that a stabilized ΔVal-containing β-hairpin is more highly folded than its Asn-containing congener.
庞大的脱氢氨基酸脱氢缬氨酸（ΔVal）和脱氢乙基正缬氨酸（ΔEnv）可以插入β-发夹肽的转角区域而不改变其二级结构。这些残基增加了蛋白水解稳定性，其中位于（i + 1）位的 ΔVal 影响最大。此外，庞大的脱氢氨基酸可以与 d-氨基酸（即 d-Pro）配对，以协同增强对蛋白水解的抗性。通过发现含有稳定的 ΔVal 的β-发夹比含有天冬酰胺的同系物更折叠来建立蛋白水解稳定性和肽结构之间的联系。
