Synthesis and biological activity of NK1 tachykinin antagonists not containing D-residues.
A series of analogues of the previously reported NK1 tachykinin antagonist [Orn6, Glu(OBzl)11]-SP6-11-OBzl has been synthesized and tested in order to investigate the effects on antagonistic activity of modifications at the C-terminal residue. The biological activity in the guinea-pig ileum assay (NK1 receptor) indicates that the two aromatic rings introduced in the C-terminal part of the peptide are both essential for the expression of antagonistic activity.
Poulos
C
C
Department of Chemistry, University of Patras, Greece.
Antoniou
M
M
Patacchini
R
R
Maggi
C A
CA
Rovero
P
P
D000595:Amino Acid Sequence; D000818:Animals; D015195:Drug Design; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D008969:Molecular Sequence Data; D015394:Molecular Structure; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects; D011817:Rabbits; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D013329:Structure-Activity Relationship; D013373:Substance P / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D018040:Receptors, Neurokinin-1; C086814:substance P (6-11)-O-benzyl, Orn(6)-Glu(O-benzyl)(11)-; C079225:substance P (6-11), Orn(6)-; D013373:Substance P