SYNTHESIS OF HUMAN CCK26-33 AND CCK-33 RELATED ANALOGS ON 2,4-DMBHA AND TMBHA

New analogues of human cholecystokinin in which the Tyr(SO3H) has been replaced by Phe(p-CH2SO3Na), methionines by norleucines, and tryptoph an by anine{[Phe(p-CH2-SO3Na)27,Nle28,31,Nal30]-CCK26-33 and [Phe(p-CH 2SO3Na)27,Nle7,28,31,Nal30]-CCK-331 were synthesized by Fmoc solid pha se methodology on two different resins (2,4-dimethoxybenzhydrylamine- and 4-(benzyloxy)-2',4'-dimethoxybenzhydrylamine resins, 2,4-DMBHA and TMBHA resins, respectively). While the syntheses on the TMBHA appeare d to be more sluggish than those carried out on the 2,4-DMBHA, both fi nal crude products were of equivalent relative purity and after purifi cation gave approximately the same final yields of analogues estimated to have a purity greater than 93 % using RPHPLC and CZE. The peptides were further characterized by amino acid analysis and LSIMS. Phe(p-CH 2SO3Na)27,Nle7,28,31,Nal30]-CCK-33 was submitted to 33 Edman cycles an d shown to be the desired product with less than 3 % preview. Both ana logues were tested for their ability to stimulate amylase release from isolated rat pancreatic acini. In this assay, [Phe(p-CH2SO3Na)27,Nle2 8,31,Nal30] -CCK26-33 and Phe(p-CH2SO3Na)27,Nle7,28,31,Nal30]-CCK-33 w ere 10 and 30 times less potent than CCK-8, respectively.