TY - JOUR
T1 - Conformationally restricted cyclic analogues of substance P
T2 - Insight into the receptor binding process
AU - Darman, Paul S.
AU - Landis, Geoffrey C.
AU - Smits, John R.
AU - Hirning, Lane D.
AU - Gulya, Karoly
AU - Yamamura, Henry I.
AU - Burks, Thomas F.
AU - Hruby, Victor J.
N1 - Funding Information:
This work was supported by U.S. Public Health Service grant NS 19972, the National Science Foundation, and awards from the University of Arizona Graduate Student Development Fund and Summer Support Program.
PY - 1985/3/15
Y1 - 1985/3/15
N2 - 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.
AB - 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.
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U2 - 10.1016/S0006-291X(85)80211-4
DO - 10.1016/S0006-291X(85)80211-4
M3 - Article
C2 - 2579658
AN - SCOPUS:0022368711
VL - 127
SP - 656
EP - 662
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -