AMINO-ACIDS AND PEPTIDES .223. SYNTHESIS AND BIOLOGICAL PROPERTIES OF CHOLECYSTOKININ HEPTAPEPTIDE ANALOGS CONTAINING D-FORMS AND L-FORMS OF TERT-LEUCINE OR NEOPENTYLGLYCINE IN POSITION-5

Using solution or solid-phase synthesis we prepared the cholecystokinin fragment Boc-CCK-7 (Boc-Tyr-(SO3-.Na+)-Met-Gly-Trp-Met-Asp-PheNH2) and its four analogues in which the methionine moiety (Met) in the carboxy-terminal part is replaced by tert-leucine (Tle) or neopentylglycine (Neo) residue or D-enantiomers of these non-coded amino acids. These structural modifications led to reduction of the studied biological activities (gall bladder contraction, anorectic activity, analgetic and sedation activity) of all prepared analogues except Boc[Neo5]--CCK-7 which, being less analgetically active, retains full gall bladder and sedation activity of CCK-8. Moreover, its anorectic activity is substantially higher (400%). This analogue is very interesting particularly for its selectively increased (4x) anorectic effect compared with that of CCK-8.