December 8, 2000

Constrained Peptidomimetics for TRH: cis-Peptide Bond Analogs

Yunsong Tong, Jacek Olczak, Janusz Zabrocki, Marvin C. Gershengorn, Garland R. Marshall and Kevin D. Moeller
Tetrahedron, 2000, 56 (50), 9791-9800

Two constrained analogs of the tripeptide hormone thyroliberin (TRH) have been synthesized. In both, the HisPro peptide bond of the hormone has been ‘locked’ into a cis-conformation. In the first analog, the constraint used was identical to the constraint used in an earlier trans-peptide bond analog that was a potent agonist for the TRH endocrine receptor TRH-R1. The second analog was built in order to take advantage of a tetrazole ring as the cis-peptide bond constraint. Neither analog showed agonist or antagonist behavior toward TRH-R1 suggesting that the cis-peptide bond conformation may not play a role in the affinity of TRH for TRH-R1.