Synthesis and biological activity of NK1 substance P selective agonists by modifying the methionyl residue.
A series of analogues of substance P, where the Met11 residue was replaced by Glu(OCH2CH3), Glu(OBzl) and Hse(CH3), were synthesized in order to investigate the effect on agonist activity of modifications at the C-terminal residue. The biological activities in the guinea-pig ileum assay (NK1 receptor) and rat [text says rabbit] pulmonary artery (NK2 receptor) indicate that replacement of the SCH3 group of Met11 of substance P by the COOBzl or OCH3 groups favour interaction with the NK1 receptor and increase selectivity towards this receptor subtype.
Poulos
C
C
Department of Chemistry, University of Patras, Greece.
Antoniou
M
M
Patacchini
R
R
Maggi
C A
CA
Pegoraro
S
S
Rovero
P
P
D000595:Amino Acid Sequence; D000818:Animals; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008715:Methionine / Q000737:chemistry*; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D011651:Pulmonary Artery; D011817:Rabbits; D051381:Rats; D018040:Receptors, Neurokinin-1 / Q000819:agonists*; D018041:Receptors, Neurokinin-2 / Q000819:agonists; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology*
D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D013373:Substance P; D008715:Methionine