Optimizing PK properties of cyclic peptides: the effect of side chain substitutions on permeability and clearance().
Optimizing PK properties of cyclic peptides: the effect of side chain substitutions on permeability and clearance().
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DOI：
10.1039/c2md20203d
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发表时间：
2012-10
期刊：
影响因子：
--
通讯作者：
Lokey RS
中科院分区：
文献类型：
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作者：
Rand AC;Leung SS;Eng H;Rotter CJ;Sharma R;Kalgutkar AS;Zhang Y;Varma MV;Farley KA;Khunte B;Limberakis C;Price DA;Liras S;Mathiowetz AM;Jacobson MP;Lokey RS
设计和制备了一系列环肽来研究影响该化学型大鼠口服生物利用度的理化特性。特别是，通过掺入肠道不同区域带电荷的天然氨基酸残基来检查肽的电离状态。此外，在各种体外测定中生成数据，并讨论了该数据在预测大鼠中观察到的后续口服生物利用度方面的有用性。
A series of cyclic peptides were designed and prepared to investigate the physicochemical properties that affect oral bioavailabilty of this chemotype in rats. In particular, the ionization state of the peptide was examined by the incorporation of naturally occurring amino acid residues that are charged in differing regions of the gut. In addition, data was generated in a variety of in vitro assays and the usefulness of this data in predicting the subsequent oral bioavailability observed in the rat is discussed.