Selective agonists of tachykinin binding sites.
Three types of binding sites for the mammalian tachykinins, ie Substance P (SP) Neurokinin A (NKA) and Neurokinin B (NKB), have been found in both the central and peripheral nervous systems. Substance P binds to the NK-1 subclass of binding site while NKA and NKB are less selective endogenous ligands, which preferentially interact with the NK-2 and NK-3 subclasses of binding sites, respectively. Complementary strategies, including 3-dimensional structure analysis by NMR spectroscopy and structure-activity relationship led to the design of selective agonists of these binding sites. [Pro9] SP, [Pro10] SP and the cyclic analogues [Cys3,6, Tyr8, Pro9] SP and [Cys3,6, Tyr8, Pro10] SP are selective NK-1 agonists. [Lys5] NKA(4-10) is a water soluble NK-2 potent agonist. Finally, [Pro7] NKB, which completely discriminates NK-2 and NK-3 binding sites, is a water-soluble NK-3 selective agonist.
Lavielle
S
S
Laboratoire de Chimie Organique Biologique, CNRS UA 493, Paris, France.
Chassaing
G
G
Loeuillet
D
D
Convert
O
O
Torrens
Y
Y
Beaujouan
J C
JC
Saffroy
M
M
Petitet
F
F
Bergström
L
L
Glowinski
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D008969:Molecular Sequence Data; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D018039:Receptors, Tachykinin; D015320:Tachykinins / Q000378:metabolism*
D017981:Receptors, Neurotransmitter; D018039:Receptors, Tachykinin; D015320:Tachykinins