SYNTHESIS AND RADIOLABELLING OF NEW ENDOMORPHIN ANALOGUES CONTAINING UNNATURAL α- AND β-AMINO ACIDS

摘要

Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2) are highly potent and selective endogenous μ-opioid receptor agonists (1). According to previous structure-activity studies, replacement of Tyr for Dmt (2', 6'-dimethyl tyrosine) resulted in potent but less selective endomorphins (2). Replacement of Pro by alicyclic β-amino acids as proline mimetics (cis-2-waminocyclopentanecarboxylic acid (Acpc) and 2-aminocyclohexenecarboxylic acid (Achc)) resulted in stable endomorphin analogues against proteolytic enzymes (3). This work focuses on new procedures of tritiated Dmt~1-endomorphin-2 isotopomers and Tyr-Acpc~2/Achc~2-endomorphin-2.