Featured Research

from universities, journals, and other organizations

In Drug Design, A Loose Fit May Be Best Bet

Date:
May 14, 2006
Source:
NIH/National Institute of Diabetes and Digestive and Kidney Diseases
Summary:
Chemical knockoffs resembling a key thyroid-related hormone are, in certain cases, more effective than the real thing at activating the target receptor, says a new study conducted in part by researchers at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Institute on Deafness and Other Communication Disorders (NIDCD), two of the National Institutes of Health (NIH).

Chemical knockoffs resembling a key thyroid-related hormone are, in certain cases, more effective than the real thing at activating the target receptor, says a new study conducted in part by researchers at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Institute on Deafness and Other Communication Disorders (NIDCD), two of the National Institutes of Health (NIH).

The improved performance is related to how closely coupled the chemical and receptor are, the scientists conclude, with a loose connection being more effective than a tight one. The findings are at odds with the widely held notion that the stronger the association between a hormone and its receptor, the more effective its cellular signaling. If the findings hold true for similar hormone-receptor reactions, they could help change the way that drug therapies are designed for a host of health problems, from smell and taste disorders to heart disease, asthma, migraine, and pain. The study is published in the May 12, 2006, issue of the Journal of Biological Chemistry.

The researchers looked at thyrotropin-releasing hormone, or TRH, a hormone released in the brain that kicks off a chain of events throughout the body, including the stimulation of the thyroid gland. As with many of the body’s hormones, cells recognize TRH using a receptor belonging to a mega-family of proteins known as G-protein-coupled receptors (GPCRs), which play a lead role in cell-to-cell communication. When a hormone binds to its designated GPCR on the outside of a cell, a specific G-protein is activated within the cell, initiating a cascade of biochemical events leading to the unique and appropriate cellular response to that hormone.

“GPCRs are the targets of roughly a third of medicines sold today, so if this finding for TRH holds for other GPCR targets, it could have significant implications for drug development,” says Marvin C. Gershengorn, M.D., director of NIDDK’s Division of Intramural Research and senior author of the paper.

“At first glance, a cellular process that affects the thyroid gland may not seem especially meaningful to the study of communication disorders,” says John Northup, Ph.D., who heads the Section on Signal Transduction of NIDCD’s Laboratory of Cellular Biology. “However this research provides information that is fundamental to cellular signaling, a function that is essential to all cells in all systems in the body, including our sensory systems of hearing, balance, taste, and smell.”

By tweaking portions of the TRH molecule, the researchers developed six slightly edited versions, while retaining most of the properties of the natural hormone. Measuring the cellular response when hormone meets receptor, they found that the lower the affinity between the two, the stronger the signal that is elicited, with certain analogs performing up to twice as effectively as TRH. As to why this would be the case, the researchers suggest that a loose connection between hormone and GPCR may allow a hormone to repetitively dock to and undock from its associated GPCR, activating a succession of G-proteins, and firing signal after signal. A tight connection, alternatively, may tie up a hormone with its GPCR, activating one G-protein, and limiting its signaling ability.

In future studies, the scientists hope to determine whether their findings are consistent with other hormone-GPCR reactions. Other researchers taking part in the study represent the National Institute of Pharmaceutical Education and Research, Punjab, India.


Story Source:

The above story is based on materials provided by NIH/National Institute of Diabetes and Digestive and Kidney Diseases. Note: Materials may be edited for content and length.


Cite This Page:

NIH/National Institute of Diabetes and Digestive and Kidney Diseases. "In Drug Design, A Loose Fit May Be Best Bet." ScienceDaily. ScienceDaily, 14 May 2006. <www.sciencedaily.com/releases/2006/05/060514082040.htm>.
NIH/National Institute of Diabetes and Digestive and Kidney Diseases. (2006, May 14). In Drug Design, A Loose Fit May Be Best Bet. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2006/05/060514082040.htm
NIH/National Institute of Diabetes and Digestive and Kidney Diseases. "In Drug Design, A Loose Fit May Be Best Bet." ScienceDaily. www.sciencedaily.com/releases/2006/05/060514082040.htm (accessed July 31, 2014).

Share This




More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

House Republicans Vote to Sue Obama Over Healthcare Law

House Republicans Vote to Sue Obama Over Healthcare Law

Reuters - US Online Video (July 31, 2014) The Republican-led House of Representatives votes to sue President Obama, accusing him of overstepping his executive authority in making changes to the Affordable Care Act. Mana Rabiee reports. Video provided by Reuters
Powered by NewsLook.com
Despite Health Questions, E-Cigs Are Beneficial: Study

Despite Health Questions, E-Cigs Are Beneficial: Study

Newsy (July 31, 2014) Citing 81 previous studies, new research out of London suggests the benefits of smoking e-cigarettes instead of regular ones outweighs the risks. Video provided by Newsy
Powered by NewsLook.com
Dangerous Bacteria Kills One in Florida

Dangerous Bacteria Kills One in Florida

AP (July 31, 2014) Sarasota County, Florida health officials have issued a warning against eating raw oysters and exposing open wounds to coastal and inland waters after a dangerous bacteria killed one person and made another sick. (July 31) Video provided by AP
Powered by NewsLook.com
Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins