Cholecystokinic activity of Nα‐hydroxysulfonyl‐[Nle^28,31]CCK_26‐33 analogues modified at the C‐terminal residue

Three new analogues of Nα‐hydroxysulfonyl‐[Nle^28,31]CCK_26‐33 are reported in which the C‐terminal l‐Phe³³ residue has been replaced by l‐Leu, d‐Phe or N‐methyl‐l‐Phe. Biological evaluation in a series of binding and bioassays demonstrates that both l‐stereochemistry and an aromatic side chain at position‐33 are essential for full agonist activity. While the l‐Leu³³ and d‐Phe³³ analogues had reduced potencies in stimulating contraction of the guinea pig ileum or gall bladder, the d‐Phe³³ analogue was fourfold selective for the ileum. This latter analogue also exhibited apparent partial agonism in the rat pancreatic amylase release assay. The N‐methyl‐l‐Phe³³ analogue was almost equipotent to the parent analogue in all bioassays, suggesting that this modification might be useful for introducing enzymatic stability in CCK analogues.