Synthesis and biological activity of Boc [Nle28, Nle31]CCK27-33, a highly potent CCK8 analogue.
A new CCK8 related peptide, Boc[Nle28,Nle31]CCK27-33 (Boc[diNle]CCK7) was synthesized and tested for cholecystokinic activity, at both the peripheral and the central level. This analogue, protected against both chemical oxidation and enzymatic degradation by aminopeptidases, was shown to be equipotent to CCK8 in releasing amylase from rat pancreas fragments. In addition, the EC50 values of Boc[diNle]CCK7 in the guinea pig gallbladder and ileum contraction assays (3.2 nM and 3.0 nM respectively) were similar to those of CCK8 (6.0 nM and 2.0 nM). Moreover both Boc[diNle]CCK7 and CCK8 elicited similar effects on the open field test over the same concentrations range. These results demonstrate the ability of Boc[diNle]CCK7 to be a suitable tool for investigating the physiological role of native CCK8.
Ruiz-Gayo
M
M
Daugé
V
V
Menant
I
I
Bégué
D
D
Gacel
G
G
Roques
B P
BP
D000681:Amylases / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D012636:Secretory Rate / Q000187:drug effects; D012844:Sincalide / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D010446:Peptide Fragments; C025997:cholecystokinin (27-33); D000681:Amylases; D012844:Sincalide