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.
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 -