Conventional theory of modern drug design challenged
October 11th, 2010 - 4:16 pm ICT by ANILondon, Oct 11 (ANI): New evidence that challenges the current theory about a process key to the way modern drugs are designed and how they work in the human body has been uncovered by the scientists from The Scripps Research Institute.
Currently, the theory about ligands - compounds that bind to proteins and trigger a specific biological action - and how they bind to proteins runs along the lines of a one person-one vote paradigm. Ligands are considered to be the relatively static partner in the process, and easily rejected if the protein dramatically changes shape.
In contrast, working with the molecular systems that recognize the hormone estrogen, the new Scripps Research study found that as protein receptors change shape ligands can adapt to that change, binding productively to both active and inactive structures.
In the current study, the scientists worked with a receptor (which binds substances triggering certain biological effects) for the hormone estrogen and a well-known estrogen receptor antagonist (which blocks the receptor).
Estrogen receptors are activated by the hormone estrogen, which is one of two primary female sex hormones (the other is progesterone). Disturbances in estrogen levels play a role in number of disorders including cancers, heart disease, and stroke in women.
When ligands bind to a specific subset of receptors, the ligands stabilize specific protein conformations, turning on (or off) molecular switches that control diverse cellular functions. For example, the binding of the breast cancer treatment tamoxifen is specific for the inactive conformation of the estrogen receptor - this locks the receptor in place, blocks the active conformation and prevents tumor growth.
“As the protein and ligand move together, each can have a unique affinity, and activity profile, which working together defines the signaling output,” the Nature quoted Kendall Nettles, an associate professor in the Department of Cancer Biology at Scripps Florida, as saying.
The new study was published October 10, 2010 in an advance, online edition of the journal Nature Chemical Biology. (ANI)
- Early warning alerts our cells against invading bugs - Oct 16, 2011
- Key to get estrogen's benefits without cancer risk found - Jun 24, 2010
- Evidence of unusual drug-resistant breast tumours found - Oct 09, 2010
- New mechanism regulating body's 24-hour clock identified - Nov 12, 2010
- Possible clues to tamoxifen resistance in breast cancer patients found - Mar 31, 2011
- Scripps finding on DNA repair brings hope to cancer patients - Mar 28, 2011
- How progesterone and estrogen increase breast cancer risk - Jan 19, 2011
- Cholesterol shows promise in fighting cancer - Apr 23, 2012
- Flower power may cut resistance to breast cancer drug tamoxifen - Feb 17, 2010
- Estrogen helps women pile on pounds - Oct 06, 2011
- Measles virus is 'the latest weapon against cancer' - Jan 13, 2011
- New way to halt expansion of breast cancer stem cells discovered - Nov 24, 2010
- Digital signal processing technique sheds light on memory and learning - Feb 08, 2011
- Drug to reverse muscle loss due to cancer created - Aug 20, 2010
- Compound that effectively suppresses multiple sclerosis developed - Apr 19, 2011
Tags: activity profile, biological action, biological effects, breast cancer, breast cancer treatment, breast cancer treatment tamoxifen, cellular functions, change shape, conventional theory, estrogen levels, estrogen receptor, estrogen receptors, female sex hormones, hormone estrogen, ligands, molecular switches, place blocks, protein conformations, receptor antagonist, scripps research institute