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  • Title: Cholecystokinin analogues with high affinity and selectivity for brain membrane receptors.
    Author: Hruby VJ, Fang SA, Knapp R, Kazmierski W, Lui GK, Yamamura HI.
    Journal: Int J Pept Protein Res; 1990 Jun; 35(6):566-73. PubMed ID: 2401597.
    Abstract:
    A series of CCK analogues in which positions 28 and 31 have been replaced by N-methylnorleucine residues have been synthesized. It has been found that most of these N-methylnorleucine containing analogues of CCK are highly potent and some are extraordinarily selective for the central vs. peripheral receptor in two animal models (guinea pig and rat). [N-MeNle28,31]CCK26-33 nonsulfated exhibited both high potency (IC50 = 0.13 nM) and selectivity for central vs. peripheral receptors. The pancrease to brain cortex binding affinity ratio for this analogue is 5100 in the rat model. NMR studies reveal that there is cis/trans isomerism about the N-methylnorleucine residue that may be related to high selectivity.
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