Low affinity binding (high levels of Ki) means that a relatively high concentration of a ligand is required before the binding site is fully occupied and the maximum physiological response to the ligand is achieved. In the example on the right, two different ligands bind to the same receptor binding site. Only one of the agonists shown can stimulate the receptor to the maximum and can therefore be defined as a complete agonist. An agonist that can only partially activate the physiological response is called a partial agonist. In this example, the concentration at which the full agonist (red curve) can activate the receptor at no more than half is about 5 x 10−9 molars (nM = nanomolars). The estrogen receptor (ER) is a ligand-inducible transcription factor composed of a central DNA-binding domain, a disrupted domain of N-terminal activation function 1 (AF1) and a C-terminal ligand binding domain (LBD). When estrogen binds to its ER, transcription is activated by recruiting various chromatin-modifying cofactors and enzymes at specific chromatin sites. Some examples of ligands that bind to RTKs include nerve growth factor (NGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and insulin. The binding of a ligand to most RTKs leads to ligand-induced dimerization of these receptors, which then leads to a process known as autophosphorylation. Radioligands are radioisotope-labelled compounds used in vivo as tracers in PET studies and for in vitro binding studies. Bonding occurs by intermolecular forces such as ionic bonds, hydrogen bonds, and van der Waals forces. The association or mooring is in fact reversible by dissociation. Irreversible and measurable covalent bonds between the ligand and the target molecule are atypical in biological systems.
Unlike the definition of ligand in organometallic and inorganic chemistry, it is not clear in biochemistry whether the ligand generally binds to a metal site, as is the case with hemoglobin. In general, the interpretation of ligands is contextual in relation to the type of binding observed. Binding affinity data alone do not determine the overall potency of a drug. Power results from the complex interaction of binding affinity and ligand activity. Ligand efficiency refers to the ligand`s ability to produce a biological response when binding to the target receptor and the quantitative magnitude of that response. This reaction can occur as an agonist, antagonist or inverse agonist, depending on the physiological response produced.  When a ligand binds to a nuclear receptor, the receptor undergoes a conformational change that prevents the ligand from dissociating from the receptor. The newly formed receptor-ligand complex can then bind to specific DNA sequences called hormonal reaction elements (HRE). There are four different types of HRE receptors, all derived from pairs of sequences with RGGTCA consensus, with the R molecule representing purine.
Bivalent ligands consist of two drug molecules (pharmacophores or ligands) connected by an inert binding agent. There are different types of bivalent ligands and are often classified based on what the pharmacophores target. Homobivalent ligands target two of the same types of receptors. Heterobivalent ligands target two different types of receptors.  Bitopic ligands target orthosteric binding sites and allosteric binding sites at the same receptor.  In scientific research, bivalent ligands have been used to study receptor dimers and their properties. This class of ligands was developed by Philip S. Portoghese and colleagues studying the opioid receptor system.    Bivalent ligands have also been reported early by Micheal Conn et al. for gonadotropin-releasing hormone receptor.   Since these initial reports, numerous bivalent ligands have been reported for various G protein-coupled receptor systems (GPCRs), including cannabinoids, serotonin, oxytocin, and melanocortin receptor systems, and for GPCR-LIC systems (D2 and nACh receptors).  Each type of biological receptor has some degree of specificity to one or at most a few ligands to bind to its ligand binding region.
Ligand-activated receptors are found both on the cell surface and at various intracellular sites. Type I HRE receptors include, for example, androgen, estrogen and progesterone receptors, all of which are anchored in the cytoplasm by chaperone proteins such as HSP90. Once a ligand binds to one of these type I receptors, the receptor is removed from the chaperone protein to allow the ligand to enter the nucleus to activate a variety of target genes. Selective ligands tend to bind to very limited types of receptors, while non-selective ligands bind to several types of receptors. This plays an important role in pharmacology, where drugs that are not selective tend to have more side effects because they bind to several other receptors, in addition to the one that produces the desired effect. These sample phrases are automatically selected from various online information sources to reflect the current use of the word “ligand”. The views expressed in the examples do not represent the views of Merriam-Webster or its editors. Send us your feedback. A ligand that can bind to the receptor and alter the function of the receptor that triggers a physiological response is called a receptor agonist. Ligands that bind to a receptor but do not activate the physiological response are receptor antagonists.
Although most ligand receptors are present on the cell surface, several different types of intracellular receptors are involved in different signaling pathways within the cell. Nuclear receptors, also known as major hormone receptors, are activated by fat-soluble molecules such as steroid hormones, thyroid hormones, retinoids, and vitamin D. In addition to ligands being studied for new therapeutic purposes, chelating agents have traditionally used ligands to prevent or reduce metal ion toxicity. For example, 2,3-dimercaptopropanol, also known as British anti-Lewisite (BAL), has been used to treat mercury poisoning for several decades. The interaction of ligands with their binding sites can be characterized in terms of binding affinity. In general, high-affinity ligand binding results from greater attractive forces between the ligand and its receptor, while ligand binding with low affinity implies weaker attraction. In general, a high-affinity bond results in higher ligand occupancy of the receptor than is the case with a low-affinity bond; Residence time (lifespan of the receptor-ligand complex) is not correlated. High-affinity binding of ligands to receptors is often physiologically important when part of the binding energy can be used to cause a conformational change in the receptor, resulting in alteration in the behavior of, for example, an ion channel or associated enzyme.
In addition to their usefulness in limiting the harmful effects of metal ion accumulation, ligands have also been used for their inhibitory effect against selected metalloenzymes or to facilitate the redistribution of certain metal ions. Another therapeutic chelating ligand includes the one used to treat hemochromatosis, a genetic disease that causes iron to build up in affected people.