二肽
化学
寡肽
炎症性肠病
并行传输
胃肠道
对映体
手性(物理)
跨细胞
运输机
药理学
肽
内科学
生物化学
立体化学
医学
疾病
膜
磁导率
基因
物理
量子力学
手征对称破缺
Nambu–Jona Lasinio模型
夸克
作者
Qikun Jiang,Qiuchi Xu,Yingli Wang,Pengyan Li,Yunran Zhang,Yongjun Wang,Jin Sun,Tianhong Zhang,Zhonggui He
标识
DOI:10.1021/acs.jmedchem.1c01276
摘要
The naturally occurring linear dipeptide JBP923 (trans-4-l-Hyp-l-Ser, HS-tLL) with anti-inflammatory effects showed potential for the treatment of inflammatory bowel disease (IBD). However, colon-specific delivery after oral administration is still a challenge because its absorption is mediated by oligopeptide transporter 1 (PEPT1) in the upper small intestine and because of its instability in the gastrointestinal tract. Therefore, we aimed to enhance the colon-targeting efficiency by modulating HS-tLL chirality to synthesize eight enantiomers. Among these enantiomers, trans-4-d-Hyp-d-Ser, cis-4-l-Hyp-d-Ser, cis-4-d-Hyp-l-Ser, and cis-4-d-Hyp-d-Ser did not work as substrates of PEPT1 and were stable in the gastrointestinal tract, resulting in enhanced colonic accumulation through the paracellular pathway due to the loose tight junctions in IBD. Interestingly, cis-4-d-Hyp-d-Ser exerted the most potent therapeutic effect on IBD. Our findings revealed the impact of chirality on the colonic accumulation of the linear dipeptide, providing strategies for the colon-targeted delivery of the linear dipeptide for the treatment of IBD.
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