Abstract

In order to examine the compatibility of a carbon bridge for restricting the conformation of the pyroglutamate region of the thyrotropin-releasing hormone (thyroliberin, TRH) with binding and activation of the TRH receptor (TRH-R), the conformationally restricted TRH analog 3 was synthesized and tested for binding, potency, and efficacy. By taking advantage of an electrochemical procedure for functionalizing pyroglutamate derivatives, analog 3 was synthesized in just six steps from pyroglutamic acid. The testing of 3 for its ability to activate TRH-R showed that the carbon bridge added to restrict the conformation of the pyroglutamate region did not seriously interfere with either binding or activation. It is clear from this work that the added carbon bridge is suitable for use in """"""""mapping"""""""" the three-dimensional requirements of the TRH-R binding site.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR000954-20
Application #
5221838
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
20
Fiscal Year
1996
Total Cost
Indirect Cost

  Publications

Yue, Xuyi; Dhavale, Dhruva D; Li, Junfeng et al. (2018) Design, synthesis, and in vitro evaluation of quinolinyl analogues for ?-synuclein aggregation. Bioorg Med Chem Lett 28:1011-1019
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Lin, Xiaobo; Racette, Susan B; Ma, Lina et al. (2017) Endogenous Cholesterol Excretion Is Negatively Associated With Carotid Intima-Media Thickness in Humans. Arterioscler Thromb Vasc Biol 37:2364-2369
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Cade, W Todd; Levy, Philip T; Tinius, Rachel A et al. (2017) Markers of maternal and infant metabolism are associated with ventricular dysfunction in infants of obese women with type 2 diabetes. Pediatr Res 82:768-775
Lucey, Brendan P; Mawuenyega, Kwasi G; Patterson, Bruce W et al. (2017) Associations Between ?-Amyloid Kinetics and the ?-Amyloid Diurnal Pattern in the Central Nervous System. JAMA Neurol 74:207-215
Mertins, Philipp; Mani, D R; Ruggles, Kelly V et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534:55-62
Murata, Takahiro; Dietrich, Hans H; Horiuchi, Tetsuyoshi et al. (2016) Mechanisms of magnesium-induced vasodilation in cerebral penetrating arterioles. Neurosci Res 107:57-62
Hölttä, Mikko; Dean, Robert A; Siemers, Eric et al. (2016) A single dose of the ?-secretase inhibitor semagacestat alters the cerebrospinal fluid peptidome in humans. Alzheimers Res Ther 8:11
Karner, Courtney M; Esen, Emel; Chen, Jiakun et al. (2016) Wnt Protein Signaling Reduces Nuclear Acetyl-CoA Levels to Suppress Gene Expression during Osteoblast Differentiation. J Biol Chem 291:13028-39

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