Constrained peptidomimetics for TRH: cis-peptide bond analogs

Two constrained analogs of the tripeptide hormone thyroliberin (TRH) have b een synthesized. In both, the HisPro peptide bond of the hormone has been ' locked' into a cis-conformation. In the first analog, the constraint used w as identical to the constraint used in an earlier trans-peptide bond analog that was a potent agonist for the TRH endocrine receptor TRH-R-1. The seco nd analog was built in order to take advantage of a tetrazole ring as the c is-peptide bond constraint. Neither analog showed agonist or antagonist beh avior toward TRH-R1 suggesting that the cis-peptide bond conformation may n ot play a role in the affinity of TRH for TRH-R1. (C) 2000 Elsevier Science Ltd. All rights reserved.