Conformationally restricted TRH analogues: Constraining the pyroglutamate region

Jill C. Simpson, Chris Ho, E. F. Berkley Shands, Marvin C. Gershengorn, Garland R. Marshall, Kevin D. Moeller

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

A modified synthetic route has been developed so that the steric size of constraints added to the pyroglutamate region of TRH (pGluHisProNH2) can be varied. Both an analogue with a smaller ethylene bridge and a larger, more flexible propane bridge in this region have been synthesized. These analogues were synthesized in order to probe why the initial incorporation of an ethane bridge into this region of the molecule had led to an analogue with a binding constant and potency three times lower than that of an directly analogous unconstrained analogue. The data for both analogues indicated that the fall off in activity caused by the ethane bridge in the initial analogue was not caused by the size of the bridge.

Original languageEnglish
Pages (from-to)291-302
Number of pages12
JournalBioorganic and Medicinal Chemistry
Volume10
Issue number2
DOIs
StatePublished - Jan 1 2002

Fingerprint Dive into the research topics of 'Conformationally restricted TRH analogues: Constraining the pyroglutamate region'. Together they form a unique fingerprint.

  • Cite this