Allosteric modulation of the dopamine receptor by conformationally constrained type VI beta-turn peptidomimetics of Pro-Leu-Gly-NH2.
A peptidomimetic of Pro-Leu-Pro-NH2, 7, possessing an indolizidinone type VI beta-turn mimic was synthesized via improved high-yielding protocols for the preparation and Cbz protection of alpha-allylproline. Bicyclic peptidomimetic 7 and spirobicylic peptidomimetic 8 enhanced the binding of [3H] N-propylnorapomorphine to dopamine receptors indicating that a type VI beta-turn is a possible bioactive conformation of the homochiral Pro-Leu-Pro-NH2 and Pro-Pro-Pro-NH 2 analogues of Pro-Leu-Gly-NH2 at the dopamine receptor allosteric regulatory site.
Vartak
Ashish P
AP
Department of Medicinal Chemistry, University of Minnesota, Minneapolis 55455-0343, USA.
Skoblenick
Kevin
K
Thomas
Nancy
N
Mishra
Ram K
RK
Johnson
Rodney L
RL
D000494:Allosteric Regulation; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry; D054836:Indolizidines / Q000138:chemical synthesis* / Q000737:chemistry; D009075:MSH Release-Inhibiting Hormone / Q000737:chemistry*; D008958:Models, Molecular; D018716:Molecular Mimicry; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D017433:Protein Structure, Secondary; D011954:Receptors, Dopamine / Q000737:chemistry*; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
C527732:6-N-(2'-pyrrolidinylcarbonyl)amino-6-(2-methylpropyl)-8a-carboxamidoindolizidine-5-one; D019086:Bridged Bicyclo Compounds, Heterocyclic; D054836:Indolizidines; D011954:Receptors, Dopamine; D013141:Spiro Compounds; D009075:MSH Release-Inhibiting Hormone; D011392:Proline