Cholecystokinic activity of Nα‐hydroxysulfonyl‐[Nle28,31]CCK26‐33 analogues modified at the C‐terminal residue

ELIZABETH E. SUGG, MARIANGELA SERRA, JENNIFER E. SHOOK, HENRY I. YAMAMURA, THOMAS F. BURKS, MURRAY KORC, VICTOR J. HRUBY

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Three new analogues of Nα‐hydroxysulfonyl‐[Nle28,31]CCK26‐33 are reported in which the C‐terminal l‐Phe33 residue has been replaced by l‐Leu, d‐Phe or N‐methyl‐l‐Phe.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.

Original languageEnglish (US)
Pages (from-to)514-519
Number of pages6
JournalInternational Journal of Peptide and Protein Research
Volume31
Issue number6
DOIs
StatePublished - Jun 1988

Fingerprint

Bioassay
Ileum
Biological Assay
Stereochemistry
Amylases
Rats
Assays
Guinea Pigs
Urinary Bladder
Ac-Nal(1)-Cpa(2)-Pal(3,6)-Arg(5)-Ala(10)-lHRH

Keywords

  • C‐terminal analogues
  • cholecystokinin
  • partial agonist
  • receptor selectivity

ASJC Scopus subject areas

  • Biochemistry

Cite this

SUGG, ELIZABETH. E., SERRA, MARIANGELA., SHOOK, JENNIFER. E., YAMAMURA, HENRY. I., BURKS, THOMAS. F., KORC, MURRAY., & HRUBY, VICTOR. J. (1988). Cholecystokinic activity of Nα‐hydroxysulfonyl‐[Nle28,31]CCK26‐33 analogues modified at the C‐terminal residue. International Journal of Peptide and Protein Research, 31(6), 514-519. https://doi.org/10.1111/j.1399-3011.1988.tb00910.x

Cholecystokinic activity of Nα‐hydroxysulfonyl‐[Nle28,31]CCK26‐33 analogues modified at the C‐terminal residue. / SUGG, ELIZABETH E.; SERRA, MARIANGELA; SHOOK, JENNIFER E.; YAMAMURA, HENRY I.; BURKS, THOMAS F.; KORC, MURRAY; HRUBY, VICTOR J.

In: International Journal of Peptide and Protein Research, Vol. 31, No. 6, 06.1988, p. 514-519.

Research output: Contribution to journalArticle

SUGG, ELIZABETHE, SERRA, MARIANGELA, SHOOK, JENNIFERE, YAMAMURA, HENRYI, BURKS, THOMASF, KORC, MURRAY & HRUBY, VICTORJ 1988, 'Cholecystokinic activity of Nα‐hydroxysulfonyl‐[Nle28,31]CCK26‐33 analogues modified at the C‐terminal residue', International Journal of Peptide and Protein Research, vol. 31, no. 6, pp. 514-519. https://doi.org/10.1111/j.1399-3011.1988.tb00910.x
SUGG, ELIZABETH E. ; SERRA, MARIANGELA ; SHOOK, JENNIFER E. ; YAMAMURA, HENRY I. ; BURKS, THOMAS F. ; KORC, MURRAY ; HRUBY, VICTOR J. / Cholecystokinic activity of Nα‐hydroxysulfonyl‐[Nle28,31]CCK26‐33 analogues modified at the C‐terminal residue. In: International Journal of Peptide and Protein Research. 1988 ; Vol. 31, No. 6. pp. 514-519.
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abstract = "Three new analogues of Nα‐hydroxysulfonyl‐[Nle28,31]CCK26‐33 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.",
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AU - SERRA, MARIANGELA

AU - SHOOK, JENNIFER E.

AU - YAMAMURA, HENRY I.

AU - BURKS, THOMAS F.

AU - KORC, MURRAY

AU - HRUBY, VICTOR J.

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N2 - Three new analogues of Nα‐hydroxysulfonyl‐[Nle28,31]CCK26‐33 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.

AB - Three new analogues of Nα‐hydroxysulfonyl‐[Nle28,31]CCK26‐33 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.

KW - C‐terminal analogues

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KW - receptor selectivity

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