Biomaterial Database

Synthesis and binding affinities of analogues of cholecystokinin-(30-33) as probes for central nervous system cholecystokinin receptors. 1987

D C Horwell, and A Beeby, and C R Clark, and J Hughes

CCK-30-33 has been identified as the minimum fragment of CCK with nanomolar affinity for the central CCK receptors, as assayed by displacement of [3H]-Boc-beta-alanyl-CCK-30-33 (pentagastrin) in homogenized mouse cerebral cortex. Examination of binding using this assay in the two series Boc-Trp-X-Phe-NH2 when X = Met-Asp (Boc-CCK-30-33), Gly-Asp, Met-Gly, and Gly-Gly and when X = (CH2)n (n = 0-4) reveals that modification of the tetrapeptide reduces affinity to a maximum of micromolar affinity (Boc-Trp-Gly-Asp-Phe-NH2; Ki = 2 X 10(-6) M), whereas in the series when n = 0 and 2 pentamolar affinity is still retained (Boc-Trp-Phe-NH2, Ki = 7 X 10(-5) M; Boc-Trp NH CH2-CH2-CO-Phe-NH2, Ki = 3 X 10(-5) M). Modification of the tetrapeptide CCK-30-33 reduces affinity 1000-fold, whereas di- and tripeptide fragments are identified that reduce affinity only a further 10-fold. This structure-activity relationship establishes a basis to design "peptoid" analogues of CCK that have therapeutic potential.

UI	MeSH Term	Description	Entries
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D011949	Receptors, Cholecystokinin	Cell surface proteins that bind cholecystokinin (CCK) with high affinity and trigger intracellular changes influencing the behavior of cells. Cholecystokinin receptors are activated by GASTRIN as well as by CCK-4; CCK-8; and CCK-33. Activation of these receptors evokes secretion of AMYLASE by pancreatic acinar cells, acid and PEPSIN by stomach mucosal cells, and contraction of the PYLORUS and GALLBLADDER. The role of the widespread CCK receptors in the central nervous system is not well understood.	CCK Receptors,Caerulein Receptors,Cholecystokinin Octapeptide Receptors,Cholecystokinin Receptors,Pancreozymin Receptors,Receptors, CCK,Receptors, Caerulein,Receptors, Pancreozymin,Receptors, Sincalide,Sincalide Receptors,CCK Receptor,CCK-4 Receptors,CCK-8 Receptors,Cholecystokinin Receptor,Receptors, CCK-4,Receptors, CCK-8,Receptors, Cholecystokinin Octapeptide,CCK 4 Receptors,CCK 8 Receptors,Octapeptide Receptors, Cholecystokinin,Receptor, CCK,Receptor, Cholecystokinin,Receptors, CCK 4,Receptors, CCK 8
D002540	Cerebral Cortex	The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.	Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D005755	Gastrins	A family of gastrointestinal peptide hormones that excite the secretion of GASTRIC JUICE. They may also occur in the central nervous system where they are presumed to be neurotransmitters.	Gastrin
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D013758	Tetragastrin	L-Tryptophyl-L-methionyl-L-aspartyl-L-phenylalaninamide. The C-terminal tetrapeptide of gastrin. It is the smallest peptide fragment of gastrin which has the same physiological and pharmacological activity as gastrin.	CCK-4,Cholecystokinin-Tetrapeptide,Gastrin Tetrapeptide,AOC-Tetragastrin,AOC-Tetrapeptide,CCK (30-33),CKK-4,Cholecystokinin (30-33),Cholecystokinin 4,AOC Tetragastrin,AOC Tetrapeptide,Cholecystokinin Tetrapeptide,Tetrapeptide, Gastrin
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D034444	Peptoids	Polymers of N-SUBSTITUTED GLYCINES containing chiral centers at the a-position of their side chains. These oligomers lack HYDROGEN BONDING donors, preventing formation of the usual intrachain hydrogen bonds but can form helices driven by the steric influence of chiral side chains.	Peptoid