Cholecystokinic activity of N alpha-hydroxysulfonyl-[Nle28,31]CCK26-33 analogues modified at the C-terminal residue.
Cholecystokinic activity of N alpha-hydroxysulfonyl-[Nle28,31]CCK26-33 analogues modified at the C-terminal residue.
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C 端残基修饰的 N α-羟基磺酰基-[Nle28,31]CCK26-33 类似物的胆囊收缩活性。
DOI：
10.1111/j.1399-3011.1988.tb00910.x
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Hruby,VJ
中科院分区：
文献类型：
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作者：
Sugg,EE;Serra,M;Shook,JE;Yamamura,HI;Burks,TF;Korc,M;Hruby,VJ
报道了三个新的N-α-羟磺酰基-[Nle28，31]CCK26-33类似物，其中C-末端-Phe33残基被取代为Byl-Leu，d-Phe或n-甲基-L-Phe。一系列结合和生物测定的生物学评价表明，立体化学和-33位的芳香族侧链对于充分的激动剂活性是必不可少的。虽然l-Leu33和d-Phe33类似物降低了刺激豚鼠回肠或胆囊收缩的能力，但Thed-Phe33类似物对回肠的选择性是四倍。后一类似物在大鼠胰腺淀粉酶释放实验中也表现出明显的部分激动性。然后-甲基-L-Phe33类似物在所有的生物测定中与母体类似物几乎等同，这表明这种修饰可能有助于在CCK类似物中引入酶的稳定性。
Three new analogues ofNα‐hydroxysulfonyl‐[Nle28,31]CCK26‐33are reported in which theC‐terminall‐Phe33residue has been replaced byl‐Leu,d‐Phe orN‐methyl‐l‐Phe. Biological evaluation in a series of binding and bioassays demonstrates that bothl‐stereochemistry and an aromatic side chain at position‐33 are essential for full agonist activity. While thel‐Leu33andd‐Phe33analogues had reduced potencies in stimulating contraction of the guinea pig ileum or gall bladder, thed‐Phe33analogue was fourfold selective for the ileum. This latter analogue also exhibited apparent partial agonism in the rat pancreatic amylase release assay. TheN‐methyl‐l‐Phe33analogue was almost equipotent to the parent analogue in all bioassays, suggesting that this modification might be useful for introducing enzymatic stability in CCK analogues.