β²-Homo-Amino Acid Scan of µ-Selective Opioid Tetrapeptide TAPP.

ABSTRACT: TAPP (H-Tyr-d-Ala-Phe-Phe-NH₂) is a potent, µ-selective opioid ligand. In order to gain further insights into pharmacophoric features of this tetrapeptide, we have performed a β²-Homo-amino acid (β²hAA) scan of the TAPP sequence. To this aim, 10 novel analogues have been synthesized and evaluated for µ-opioid and δ-opioid receptor affinity as well as for stability in human plasma. The derivatives included compounds in which a (R)- or (S)-β²-Homo-Homologue replaced the amino acids in the TAPP sequence. The derivatives with (R)- or (S)-β²hPhe⁴ turned out to bind µOR with affinities equal to that of the parent. β²hAAs in position 1 and 3 resulted in rather large affinity decr

SUBMITTER: Tymecka D 

PROVIDER: S-EPMC7288052 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature