Amino acids with amphiphilic side chains: Deltorphin analogues with Phe³ replaced by all β-hydroxyphenylalanine diastereoisomers

Using the method of conformational constraint, we have designed and synthesized analogues of deltorphin I containing each of the four stereoisomers of the unusual amphiphilic amino acid β-hydroxyphenylalanine in position 3. The potency and selectivity of these analogues were evaluated by radioreceptor binding assays and by bioassay in MVD and GPI. The results show that introducing a hydrophilic group into the β-carbon of Phe³ decreases the affinity and biological activity of δ-opioid receptors, which strongly depend on the chirality of the α-carbon, but not on that of the β-carbon.