Importance of Terminal Amino Acid Residues to the Transport of Oligopeptides across the Caco-2 Cell Monolayer
Importance of Terminal Amino Acid Residues to the Transport of Oligopeptides across the Caco-2 Cell Monolayer
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DOI：
10.1021/acs.jafc.7b03450
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发表时间：
2017-09-06
影响因子：
6.1
通讯作者：
Liu, Jingbo
中科院分区：
文献类型：
--
作者：
Ding, Long;Wang, Liying;Liu, Jingbo
本文的目的是研究末端氨基酸对低聚肽在Caco-2细胞单层上的运输的影响。设计阿拉基四肽和五肽，用不同的氨基酸取代N端或c端氨基酸残基。结果表明，这些寡肽在Caco-2细胞单层上具有广泛的转运通透性，可分为非/差通透性、低通透性、中等通透性和良好通透性四类。n端为Leu、Pro、Ile、Cys、Met、Val或c端为Val的四肽具有最高的通透性，其表观通透系数（p -app）大于10 × 10(-6) cm/s (p < 0.05)，表明非极性疏水脂肪氨基酸或极性含硫氨基酸最适合四肽的转运。N端或c端Tyr的五肽也表现出高通透性，P-app值约为10 × 10(-6) cm/s。氨基酸Glu、Asn和Thr在N端，赖氨酸、Asp和Arg在C端也有利于四肽和五肽的运输，其P-app值在1 × 10（-6）到10 × 10(-6) cm/s之间。此外，N端氨基酸被替换的肽的通透性普遍高于C端氨基酸被替换的肽（p < 0.05），这表明N端氨基酸对低聚肽在Caco-2细胞单层中的转运更为重要。
The objective of this paper was to investigate the effects of terminal amino acids on the transport of oligopeptides across the Caco-2 cell monolayer. Ala-based tetra- and pentapeptides were designed, and the N- or C-terminal amino acid residues were replaced by different amino acids. The results showed that the oligopeptides had a wide range of transport permeability across the Caco-2 cell monolayer and could be divided into four categories: non-/poor permeability, low permeability, intermediate permeability, and good permeability. Tetrapeptides with N-terminal Leu, Pro, Ile, Cys, Met, and Val or C-terminal Val showed the highest permeability, with apparent permeability coefficient (P-app) values over 10 X 10(-6) cm/s (p < 0.05), suggesting that nonpolar hydrophobic aliphatic amino acids or polar sulfur-containing amino acids were the best for the transport of tetrapeptides. Pentapeptides with N- or C-terminal Tyr also showed high permeability levels, with P-app values of about 10 X 10(-6) cm/s. The amino acids Glu, Asn, and Thr at the N terminus or Lys, Asp, and Arg at the C terminus were also beneficial for the transport of tetra- and pentapeptides, with P-app values ranging from 1 X 10(-6) to 10 X 10(-6) cm/s. In addition, peptides with amino acids replaced at the N terminus generally showed higher permeability than those with amino acids replaced at the C terminus (p < 0.05), suggesting that N-terminal amino acids were more important for the transport of oligopeptides across the Caco-2 cell monolayer.