Chemistry: analytical and immunological testing – Biospecific ligand binding assay
Patent
1986-12-22
1989-05-23
Marantz, Sidney
Chemistry: analytical and immunological testing
Biospecific ligand binding assay
436518, 436543, 436548, G01N 3353, G01N 33543, G01N 33577
Patent
active
048330922
DESCRIPTION:
BRIEF SUMMARY
This invention relates to a method of detecting or determining a sequence of monomer molecules which corresponds to the ligand molecule for a particular receptor. The sequence of monomer molecules so determined is the mimotope (defined below) of the particular ligand. The mimotope which is determined by this method may not have any obvious or direct relationship to the natural ligand molecule, but will share with it the ability to react with the receptor, and indeed, the mimotope so determined may be modified to incorporate specific or additional properties in the reaction with the receptor. Such a mimotope could then be used to replace the natural ligand in the treatment or prevention of particular disease or it may be used to mediate a particular biological effect.
As used throughout this specification, the terms listed below have the following meanings:
receptor: a molecule or molecular complex which will combine specifically with its particular ligand molecule. It is those receptors which on binding with their particular ligand(s) mediate a biological function that are of most interest. Examples of receptors include, but are not restricted to, the common class of receptors associated with the surface membrane of cells and include, for instance, the immunologically important receptors of B-cells, T-cells, macrophages and the like. Another example is receptors for acetyl choline on nerve cells which cause a nerve pulse to be transmitted down the length of the neuron when the receptor molecule reacts with its ligand, acetyl choline.
epitope: the specific surface of an antigen molecule which is delineated by the area of interaction with the sub-class of receptors known as antibodies.
catamer: a polymer molecule which is a precisely defined linear sequence formed by the condensation of small molecules. Note that this term includes molecules in which different types of condensation reactions are used to join the small molecules. A number prefixed to the word "catamer" implies that the catamer is formed by the condensation of the indicated number of small molecules, for example, 8-catamer means that the catamer is made up from eight small molecules. Examples of catamers include any given peptide and any given oligo-saccharide.
monomer: a member of the set of small molecules which can be condensed together to form a catamer. The set of monomers includes but is not restricted to, for example, the set of common L-amino acids, the set of D-amino acids, the set of synthetic amino acids, the set of nucleotides, and the set of pentoses and hexoses.
peptide: a catamer in which the small molecules are alpha-amino acids and which are joined together through a peptide bond. In the context of this specification it should be appreciated that the amino acids may be the L-optical isomer or the D-optical isomer.
mimotope: a catamer which in at least one of its conformations has a surface region with the equivalent molecular topology to the binding surface of the ligand molecule of which it is the mimic. In the context of immunological receptors, the mimotope mimics the epitope of the antigen.
complementary: refers to the matching together of the reacting surfaces of an ligand molecule and its receptor. Thus, the receptor and its ligand can be described as complementary, and furthermore, the contact surface characteristics are complementary to each other.
paratope: the combining site of an antibody which is complementary to a particular epitope.
ligand molecule: is the molecule which binds to a particular receptor and when bound to it mediates the biological function associated with that particular receptor.
Examples of receptors which can be investigated by this method include, but are not restricted to:
hormone receptors: for instance the receptors for insulin and Growth Hormone; determination of the mimotopes of the ligands binding to these receptors may lead to the development of an oral replacement of the daily injections which diabetics must take to relieve the symptoms of diabetes, and in the other case, a replacement
REFERENCES:
patent: 4554101 (1985-11-01), Hopp
Hopp, Thomas P. et al., Proc. Natl. Acad. Sci., U.S.A., 78(6), 3824-3828 (Jun. 1981).
Geysen, H. Mario et al., Molecular Immunology, 23(7), 709-715 (1986).
Scientific American, Feb. 1983, pp. 48-56, (p. 50, lines 33-39), R. A. Lerner, "Synthetic Vaccines".
Commonwealth Serum Laboratories Commission
Marantz Sidney
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