The design of a new potent and selective ligand for the orphan bombesin receptor subtype 3 (BRS3).
Extensive SAR studies on the unselective BRS3 agonist, [H-D-Phe6,beta-Ala11,Phe13,Nle14]-bombesin-(6-14)-nonapeptide amide, have highlighted structural features important for BRS3 activity and have provided guidance as to the design of selective agonists. A radically modified heptapeptide agonist, maintaining only the Trp-Ala moiety of the parent [H-D-Phe6,betaAla11,Phe13,Nle14]-peptide amide, and with a very different carboxyl terminal region, has been produced which was potent at BRS3 and essentially had no NMB or GRP receptor activity. Its structure is Ac-Phe-Trp-Ala-His(tauBzl)-Nip-Gly-Arg-NH2.
Boyle
Robert G
RG
Astex Technology Ltd, Cambridge, UK. b.boyle@astex-technology.com
Humphries
John
J
Mitchell
Tim
T
Showell
Graham A
GA
Apaya
Robert
R
Iijima
Hiroaki
H
Shimada
Hiroshi
H
Arai
Tomonori
T
Ueno
Hiroaki
H
Usui
Yoshihiro
Y
Sakaki
Toshiro
T
Wada
Etsuko
E
Wada
Keiji
K
D000595:Amino Acid Sequence; D000818:Animals; D001839:Bombesin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D002460:Cell Line; D015195:Drug Design; D006801:Humans; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D018004:Receptors, Bombesin / Q000819:agonists* / Q000378:metabolism*; D013379:Substrate Specificity
D008024:Ligands; D018004:Receptors, Bombesin; C107120:bombesin receptor subtype 3; D001839:Bombesin