Biomaterial Database

Receptor-specific somatostatin analogs: correlations with biological activity. 1996

D H Coy, and J E Taylor

Department of Medicine, Tulane University Medical Center, New Orleans, LA 70112-2699, USA.

A number of cyclic and linear somatostatin (SRIF) analogs have now been found to have promising levels of selectivity for rodent somatostatin receptors (rsst2,3,5), but not sst1 and sst4. Comparisons between binding affinities for these and transfected human receptors are just beginning to emerge and we present results from a comparison of affinities of several key families of peptides for sst2 present on rat AR42J cells and on cells transfected with human (h)sst2. The typical cyclic octapeptide analogs, octreotide, lanreotide, and RC-160, exhibited similar affinities to SRIF for rsst2, but somewhat lower affinities for the human receptor. Affinities of several analogs for transfected hsst5 were also measured. As with the rat receptor, octreotide-related analogs had low affinity for hsst5. The highly specific rsst5 analog, DC-23-99, was less so for the human receptor; however, a D-Tyr1 version of DC-23-99 had subnanomolar affinity (Ki, 0.68 nmol/L) and high selectivity. A new extended-ring analog, BIM-23268D, showed superior affinity to DC-23-99 and even to SRIF and SRIF-28 for hsst5 (K(i), 0.38 nmol/L), and had the highest sst5/sst2 selectivity ratio of any analog that we have tested thus far.

UI	MeSH Term	Description	Entries
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
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
D001667	Binding, Competitive	The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.	Competitive Binding
D013004	Somatostatin	A 14-amino acid peptide named for its ability to inhibit pituitary GROWTH HORMONE release, also called somatotropin release-inhibiting factor. It is expressed in the central and peripheral nervous systems, the gut, and other organs. SRIF can also inhibit the release of THYROID-STIMULATING HORMONE; PROLACTIN; INSULIN; and GLUCAGON besides acting as a neurotransmitter and neuromodulator. In a number of species including humans, there is an additional form of somatostatin, SRIF-28 with a 14-amino acid extension at the N-terminal.	Cyclic Somatostatin,Somatostatin-14,Somatotropin Release-Inhibiting Hormone,SRIH-14,Somatofalk,Somatostatin, Cyclic,Somatotropin Release-Inhibiting Factor,Stilamin,Somatostatin 14,Somatotropin Release Inhibiting Factor,Somatotropin Release Inhibiting Hormone
D017481	Receptors, Somatostatin	Cell surface proteins that bind somatostatin and trigger intracellular changes which influence the behavior of cells. Somatostatin is a hypothalamic hormone, a pancreatic hormone, and a central and peripheral neurotransmitter. Activated somatostatin receptors on pituitary cells inhibit the release of growth hormone; those on endocrine and gastrointestinal cells regulate the absorption and utilization of nutrients; and those on neurons mediate somatostatin's role as a neurotransmitter.	Receptors, Somatotropin Release Inhibiting Hormone,Somatostatin Receptors,Receptors, SRIH,SRIH Receptors,Somatostatin Receptor,Receptor, Somatostatin
D051381	Rats	The common name for the genus Rattus.	Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus