title: Structure-activity studies on the C-terminal hexapeptide of substance P with modifications at the glutaminyl and methioninyl residues.
abstract: Analogues of [Orn6]-SP6-11 have been synthesized in which the SCH3 group of the Met11 side chain is replaced by other functional groups, such as (CH2)2NH2, COOH, CONH2, and COOR, which have basic, acid, or neutral character and which may act as either H-bonding donors or H-bonding acceptors. These analogues were tested in guinea pig ileum and rat colon muscularis mucosae, in vitro. Substitution of Lys, Gln, or Glu at position 11 caused a marked reduction in biological activity in both tissues. In contrast, the glutamate benzyl ester analogue had only slightly reduced activity in the guinea pig ileum and an increased (4.7 times) activity in the rat colon. It is concluded that charged groups in the side chain at position 11 of SP6-11 reduce the biological activity of SP hexapeptide.
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D005973:Glutamine; D006168:Guinea Pigs; D008715:Methionine; D009130:Muscle, Smooth / Q000187:drug effects; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D013373:Substance P / Q000494:pharmacology*
chemical_list: D009842:Oligopeptides; D005973:Glutamine; D013373:Substance P; D008715:Methionine