Ligand (biochemistry)

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In biochemistry and related sciences, a ligand is a substance that can specifically bind to a target protein , for example a receptor . The binding of the ligand is usually reversible and is made possible in particular by ionic bonds , hydrogen bonds , van der Waals forces and hydrophobic effects . The affinity of a ligand for the target protein can be determined with the help of ligand binding tests .

properties

In contrast to substrates, ligands are not converted by the target molecule, but they can influence its three-dimensional structure and its function. Ligands that activate a receptor are called agonists , while ligands that inhibit or deactivate a receptor but do not themselves trigger a pharmaceutical effect are called antagonists . Ligands which lead to an opposite effect on a receptor are called inverse agonists . With regard to the binding site on the target protein, a distinction is made between orthosteric and allosteric ligands. Co-ligands act in concert. A high affinity bond follows the key-lock principle .

A distinction is made between the following types of chemical bonding:

  • non-covalent, reversible: most common type of bond, determined by association and dissociation
  • non-covalent, pseudo-irreversible: very slow dissociation; E.g. methyllycaconitine
  • covalent, irreversible: the ligand contains a reactive functional group; E.g. MAO inhibitors such as tranylcypromine . The target protein usually loses its function
  • covalent, reversible: e.g. a series of tear gases ; here binding of an electrophile through reaction with the thiol group of cysteine in TRPA1 , the delivery takes place through elimination reaction and leaves the target protein functional.
  • covalent, fragmented: a rare special case. The ligand binds covalently to the target protein via a reaction center of the ligand and eliminates a part of the molecule via another reaction center (“perforation point”), which then dissociates. This was experimentally realized for a DAT ligand which, according to this principle, leaves a small molecule fragment covalently bound in the DAT. Bulky molecules like cocaine are blocked from accessing the DAT, while smaller molecules like dopamine are still taken up by the DAT.

Web links

Wiktionary: Ligand  - explanations of meanings, word origins, synonyms, translations

Individual evidence

  1. Bruce Alberts et al .: Molecular Biology of the Cell , 4th ed. 2002. Available online via the NCBI bookshelf . Definition of ligand .
  2. Harvey Lodish, A. Berk, SL Zipursky , et al .: Molecular Cell Biology , 4th ed. 2000, WH Freeman, New York. Available online via the NCBI bookshelf . Definition of ligand .
  3. Meltzer PC, Liu S, Blanchette H, Blundell P, Madras BK: Design and synthesis of an irreversible dopamine-sparing cocaine antagonist . In: Bioorganic & Medicinal Chemistry . 10, No. 11, 2002, pp. 3583-91. PMID 12213473 .