Consecutive Ribosomal Incorporation of α-Aminoxy/α-Hydrazino Acids with L/D-Configurations into Nascent Peptide Chains
Consecutive Ribosomal Incorporation of α-Aminoxy/α-Hydrazino Acids with L/D-Configurations into Nascent Peptide Chains
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DOI：
10.1021/jacs.1c09270
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发表时间：
2021-11-03
影响因子：
15
通讯作者：
Suga, Hiroaki
中科院分区：
文献类型：
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作者：
Katoh, Takayuki;Suga, Hiroaki
α-氨氧基和α-肼酸是β-氨基酸类似物，其中β-碳分别被氧和氮取代。这些杂原子决定肽折叠成称为伪伽玛转角的特定二级结构。非手性 α-氨氧基乙酸 ((NO)Gly) 和 L-α-肼基苯丙氨酸 (L-(NN)Phe) 已被证明适合在核糖体翻译过程中单一掺入，但核糖体是否耐受具有 L/D 配置的其他类型的 α-氨氧基/α-肼酸尚不清楚。此外，是否可以多次或连续合并仍不清楚。我们首次展示了具有L/D构型的α-氨氧基/α-肼酸多次且连续地掺入到各种模型肽中，包括大环肽支架。
alpha-Aminoxy and alpha-hydrazino acids are beta-amino acid analogs with beta-carbons replaced by oxygen and nitrogen, respectively. Such heteroatoms dictate the folding of peptides into specific secondary structures called pseudo-gamma-turns. Achiral alpha-aminoxyacetic acid ((NO)Gly) and L-alpha-hydrazinophenylalanine (L-(NN)Phe) have been shown to be suitable for single incorporation during ribosomal translation, but whether ribosomes tolerate other types of alpha-aminoxy/alpha-hydrazino acids with L/D-configurations is unknown. Moreover, whether multiple or consecutive incorporations are possible remains unclear. We show, for the first time, multiple and consecutive incorporations of alpha-aminoxy/alpha-hydrazino acids with L/D-configurations into various model peptides, including macrocyclic peptide scaffolds.