A tetradecapeptide somatostatin dicarba-analog: Synthesis, structural impact and biological activity. 2014

Pablo Martín-Gago, and Rosario Ramón, and Eric Aragón, and Jimena Fernández-Carneado, and Pau Martin-Malpartida, and Xavier Verdaguer, and Pilar López-Ruiz, and Begoña Colás, and María Alicia Cortes, and Berta Ponsati, and Maria J Macias, and Antoni Riera
Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac, 10, 08028 Barcelona, Spain.

We described here the first tetradecapeptide somatostatin-analogue where the disulfide bridge has been replaced by a carbon-carbon double bond. This analogue was prepared using microwave assisted ring closing metathesis (RCM) using the 2nd generation Grubbs as catalyst. Under our optimized conditions the cyclization between allylGly 3 and 14 proceeded in moderate yield, excellent cyclic/linear ratio and very high Z-double bond selectivity. NMR studies also demonstrated that the conformational flexibility of this peptide is increased in comparison to that of the natural hormone. Remarkably, this alkene-bridged somatostatin analog is highly selective against somatostatin receptors 1 and 5, suggesting that conformational rigidity is not required for the efficient interaction of somatostatin analogues with these two receptors.

UI MeSH Term Description Entries
D008872 Microwaves That portion of the electromagnetic spectrum from the UHF (ultrahigh frequency) radio waves and extending into the INFRARED RAYS frequencies. EHF Waves,Extremely High Frequency Radio Waves,Micro Wave,Micro Waves,Ultrahigh Frequency Waves,Microwave Radiation,EHF Wave,Micro Waves,Microwave,Microwave Radiations,Radiation, Microwave,Ultrahigh Frequency Wave,Wave, EHF,Wave, Micro,Wave, Ultrahigh Frequency,Waves, Micro
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
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
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
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
D015394 Molecular Structure The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. Structure, Molecular,Molecular Structures,Structures, Molecular
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

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