title: Conformationally restricted cyclic analogues of substance P: insight into the receptor binding process.
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 [Cys5, Cys11]-SP5-11-NH2 and [Cys6, Cys11]-SP5-11-NH2 were inactive at concentrations up to 100 microM, while [Cys5, Cys6, Nle11]-SP was a weak agonist. The order of relative affinities on the rat brain radioreceptor assay was as follows: [Cys5, Cys6, Nle11]-SP greater than [Cys5, Cys11]-SP5-11-NH2 greater than [Cys6, Cys11]-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.
authors.forename: P S
authors.initials: PS
authors.lastname: Darman
authors.forename: G C
authors.initials: GC
authors.lastname: Landis
authors.forename: J R
authors.initials: JR
authors.lastname: Smits
authors.forename: L D
authors.initials: LD
authors.lastname: Hirning
authors.forename: K
authors.initials: K
authors.lastname: Gulya
authors.forename: H I
authors.initials: HI
authors.lastname: Yamamura
authors.forename: T F
authors.initials: TF
authors.lastname: Burks
authors.forename: V J
authors.initials: VJ
authors.lastname: Hruby
mesh_terms: D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000378:metabolism; D011487:Protein Conformation; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013373:Substance P / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism
chemical_list: D010456:Peptides, Cyclic; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D013373:Substance P