Conformationally restricted cyclic analogues of substance P

Insight into the receptor binding process

Paul S. Darman, Geoffrey C. Landis, John R. Smits, Lane D. Hirning, K. Gulya, Henry I. Yamamura, Thomas F. Burks, Victor J. Hruby

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Three new cyclic substance P analogues were prepared to examine the possible role of a pseudocyclic turn structure for receptor recognition. In the guinea pig isolated ileum [Cy over(over(s5, C, {top square bracket}),) ys11]-SP5-11 - NH2 and [Cy over(over(s6, C, {top square bracket}),) ys11]-SP5-11 - NH2 were inactive at concentrations up to 100 μM, while [Cy over(over(s5, C, {top square bracket}),) ys6, Nle11] - SP was a weak agonist. The order of relative affinities on the rat brain radioreceptor assay was as follows: [Cy over(over(s5, C, {top square bracket}),) ys6, Nle11] - SP> [Cy over(over(s5, C, {top square bracket}),) ys11] - SP5-11 - NH2 > [Cy over(over(s6, C, {top square bracket}),) ys11] - SP5-11 - NH2. We interpret these results to indicate that a pseudocyclic structure of the 5-11 sequence may not be an important factor involved in the receptor recognition of substance P.

Original languageEnglish
Pages (from-to)656-662
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume127
Issue number2
DOIs
Publication statusPublished - Mar 15 1985

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Neurokinin-1 Receptors
Radioligand Assay
Substance P
Ileum
Guinea Pigs
Brain
Rats
Assays

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Conformationally restricted cyclic analogues of substance P : Insight into the receptor binding process. / Darman, Paul S.; Landis, Geoffrey C.; Smits, John R.; Hirning, Lane D.; Gulya, K.; Yamamura, Henry I.; Burks, Thomas F.; Hruby, Victor J.

In: Biochemical and Biophysical Research Communications, Vol. 127, No. 2, 15.03.1985, p. 656-662.

Research output: Contribution to journalArticle

Darman, Paul S. ; Landis, Geoffrey C. ; Smits, John R. ; Hirning, Lane D. ; Gulya, K. ; Yamamura, Henry I. ; Burks, Thomas F. ; Hruby, Victor J. / Conformationally restricted cyclic analogues of substance P : Insight into the receptor binding process. In: Biochemical and Biophysical Research Communications. 1985 ; Vol. 127, No. 2. pp. 656-662.
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