Synthesis and biological studies of novel neurotensin(8-13) mimetics.
Novel neurotensin (NT) (8-13) (Arg(8)-Arg(9)-Pro(10)-Tyr(11)-Ile(12)-Leu(13)) mimetics 3, 4 were designed by adopting all intrinsic functional groups of the native neurotensin(8-13) and using a substituted indole as a template to mimic the pharmacophore of NT(8-13). Biological studies at subtype 1 of the NT receptor showed that 3 has a 55 and 580 nM binding affinity at rat and human neurotensin receptors, respectively. As a comparison, compounds 5 and 6 were also synthesized. The binding difference between 3, 4 and 5, 6 argues the importance of the carboxylic group in achieving higher potency NT(8-13) mimetics.
Hong
Feng
F
Neuropsychopharmarcology Research, Mayo Clinic Jacksonville, 4500 San Pablo Road, FL 32224, USA.
Zaidi
Javid
J
Cusack
Bernadette
B
Richelson
Elliott
E
D000818:Animals; D006801:Humans; D007211:Indoles / Q000737:chemistry; D018716:Molecular Mimicry; D009496:Neurotensin / Q000138:chemical synthesis* / Q000494:pharmacology*; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D018028:Receptors, Neurotensin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry*; D013329:Structure-Activity Relationship
D007211:Indoles; D010446:Peptide Fragments; D018028:Receptors, Neurotensin; C114036:neurotensin type 1 receptor; D009496:Neurotensin; C054381:neurotensin (8-13)