The present invention provides new methods, particularly computational methods, and compositions for the generation of nuclear receptor synthetic ligands based on the three dimensional structure of nuclear receptors, particularly the thyroid receptor (herein referred to as “TR”). Also provided are crystals, nuclear receptor synthetic ligands, and related methods.

Nuclear receptor ligands and ligand binding domains

Thyroid hormone (T(3)) activates nuclear receptor transcription factors, encoded by the TRalpha (NR1A1) and TRbeta (NR1A2) genes, to regulate target gene expression. Several TR isoforms exist, and studies of null mice have identified some unique functions for individual TR variants, although considerable redundancy occurs, raising questions about the specificity of T(3) action. Thus, it is not known how diverse T(3) actions are regulated in target tissues that express multiple receptor variants. I have identified two novel TRbeta isoforms that are expressed widely and result from alternative mRNA splicing. TRbeta3 is a 44.6-kDa protein that contains an unique 23-amino-acid N terminus and acts as a functional receptor. TRDeltabeta3 is a 32.8-kDa protein that lacks a DNA binding domain but retains ligand binding activity and is a potent dominant-negative antagonist. The relative concentrations of beta3 and Deltabeta3 mRNAs vary between tissues and with changes in thyroid status, indicating that alternative splicing is tissue specific and T(3) regulated. These data provide novel insights into the mechanisms of T(3) action and define a new level of specificity that may regulate thyroid status in tissue.

Cloning and Characterization of Two Novel Thyroid Hormone Receptor β Isoforms

Objective: To determine the genetic and clinical features of resistance to thyroid hormone in a study from a single institution. Design: Prospective, controlled study. Setting: National Institutes ...

Genetic and Clinical Features of 42 Kindreds with Resistance to Thyroid Hormone: The National Institutes of Health Prospective Study

The syndromes of reduced sensitivity to thyroid hormone.

Current literature makes a distinction between two pathways for thyroid hormone signaling: genomic and nongenomic. However, this classification is a source of confusion. We propose a clarification in the nomenclature that may help to avoid unproductive controversies and favor progress in this field of research. Four types of thyroid hormone signaling are defined, and the experimental criteria for classification are discussed.

/pdf/thyroid-hormone-signaling-pathways-time-for-a-more-precise-w0f591liol.pdf

Thyroid Hormone Signaling Pathways: Time for a More Precise Nomenclature

Nomenclature of thyroid hormone receptor beta-gene mutations in resistance to thyroid hormone: consensus statement from the first workshop on thyroid hormone resistance, July 10-11, 1993, Cambridge, United Kingdom

Resistance to thyroid hormone (RTH) is usually dominantly inherited and characterized by elevated thyroid hormone levels together with reduced central and peripheral tissue responsiveness to hormone action. Following linkage of this disorder to the thyroid hormone receptor P (TRP) gene locus (l), a number of studies have identified TRP mutations in RTH. Cloning of the cDNA encoding human TRPl (2) initially suggested an open reading frame of 450 amino acids. However, subsequent sequencing of this cDNA as well as genomic clones show a guanine rather than adenine at nucleotide position 288, generating a new initiation codon (3) and leading to a predicted protein sequence which contains 461 amino acids, In addition, the exons of the TRP gene have been numbered either from 00 to 8 or from 1 to 10, depending on the designation of non-coding exons. Publications to date have used both notations to describe TRP mutations leading to confusion. To avoid this, we suggest that the following nomenclature be adopted henceforth:

Nomenclature of thyroid hormone receptor μ gene mutations in resistance to thyroid hormone: consensus statement from the First Workshop on Thyroid Hormone Resistance, 10–11 July 1993, Cambridge, UK

Nomenclature of thyroid hormone receptor beta gene mutations in resistance to thyroid hormone: consensus statement from the first workshop on thyroid hormone resistance, July 10-11th 1993, Cambridge, U.K.

Nomenclature of thyroid hormone receptor ß gene mutations in resistance to thyroid hormone First Workshop on Thyroid Hormone Resistance, July 10–11, 1993, Cambridge, U.K.

Nomenclature of thyroid hormone receptor-β gene mutations in resistance to thyroid hormone: Consensus statement from the first Workshop on Thyroid Hormone Resistance, 10-11th July 1993, Cambridge, UK

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

B. D. Weintraub

Author Tools

Chat about Author