CONFORMATIONAL DETERMINANTS OF HIGH-AFFINITY DELTA-RECEPTOR BINDING OF OPIOID-PEPTIDES

  • 1 May 1988
    • journal article
    • research article
    • Vol. 33  (5) , 528-536
Abstract
Detailed conformational analysis of linear and cyclic .delta.-selective opioid peptides was performed in conjunction with computer-analyzed receptor binding studies with the aim of determining conformational requirements for high binding of peptides to the .delta.-receptor. The four linear .delta.-selective hexapeptides included in this study were: DSLET (Tyr-D-Ser-Gly-Phe-Leu-Thr) and its D-Thr2 analog (DTLET) and tow t-butyl ether analogs. In one analog an O-t-butyl group replaces the D-Ser2OH and in the other a second O-t-butyl group replaces the D-Thr6OH group as well. This study also includes seven cylcic pentapeptides of the type: Tyr-Cys(Pen-Gly-Pen-Gly-Phe-Cys)(Pen) with various combinations of DL-cysteine and DL-penicillamine (.beta.-dimethyl cysteine) as the second and fifth residues resulting in varying .delta. affinities and selectivities. Four (DPLPE, DPDPE, DPLC and DCLPE) have both high .delta. affinity and selectivity; two (DCDCE and DCLCE) have high affinity at both .delta.- and .mu.-receptors, and one (LCLCE) has low affinity for both receptors. Our investigation has shown that all analogs that have high affinity at the .delta. receptor have a unique common low energy conformer. This compact conformer contains intramolecular H-bonds and is very different from the .beta.II-turn-type structure associated with high affinity .mu.-receptor binding deduced in our previous work.

This publication has 0 references indexed in Scilit: