TETRAPEPTIDE CCK-A AGONISTS - EFFECT OF BACKBONE N-METHYLATIONS ON IN-VITRO AND IN-VIVO CCK ACTIVITY

N-Methylation of backbone amide bonds was conducted on a tetrapeptide that had been identified previously (Shiosaki, K.; et al. J. Med. Chem . 1991, 34, 2387-2842) as a potent and selective CCK-A agonist. N-alph a-Methylation at the position corresponding to Asp(32) (CCK-33 numberi ng) was consistent with high affinity, efficacy, and selectivity for t he CCK-A receptor. Combination of this (N-Me)Asp with the (N-Me)Phe mo dification also provided a highly active analogue. The observation of parallel structure-binding affinity profiles with respect to sites of N-methylation in the C-terminal regions of tetrapeptide vs heptapeptid e CCK analogues suggests that the two series interact similarly with t he CCK-A receptor.