Synthesis of a potent agonist of substance P by modifying the methionyl and glutaminyl residues of the C-terminal hexapeptide of substance P. Structure-activity relationships. 1991

K Karagiannis, and A Manolopoulou, and G Stavropoulos, and C Poulos, and C C Jordan, and R M Hagan
Department of Chemistry, University of Patras, Greece.

Analogues of [Orn6]-SP6-11 have been synthesized in which the Met11 residue is replaced by glutamate gamma-alkylesters. These analogues were tested in three in vitro preparations representative of NK-1, NK-2, and NK-3 receptor types. Substitution of the SCH3 group of the Met11 side chain by a COOR (R = methyl, ethyl, n-propyl, n-butyl, cyclohexyl) group results in analogues which are full agonists in NK-1 and NK-2 preparations but show little agonist activity in the NK-3 preparation. When the SCH3 group is replaced by a t-butyl ester group and the resulting analogue is a full agonist in all the above preparations and more active than the parent hexapeptide and SP-OCH3 at NK-1 receptors. It is concluded that for activity at NK-1 receptors methionine can be replaced by gamma-t-butyl glutamate without loss of activity, whilst at NK-2 and NK-3 receptors the above substitution increases the activity of [Orn6]-SP6-11. Other gamma-alkyl esters of the glutamic acid reduce its biological activity.

UI MeSH Term Description Entries
D007082 Ileum The distal and narrowest portion of the SMALL INTESTINE, between the JEJUNUM and the ILEOCECAL VALVE of the LARGE INTESTINE.
D008715 Methionine A sulfur-containing essential L-amino acid that is important in many body functions. L-Methionine,Liquimeth,Methionine, L-Isomer,Pedameth,L-Isomer Methionine,Methionine, L Isomer
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
D010446 Peptide Fragments Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques. Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D011169 Portal Vein A short thick vein formed by union of the superior mesenteric vein and the splenic vein. Portal Veins,Vein, Portal,Veins, Portal
D011761 Pyrrolidonecarboxylic Acid A cyclized derivative of L-GLUTAMIC ACID. Elevated blood levels may be associated with problems of GLUTAMINE or GLUTATHIONE metabolism. 5-Oxoproline,Pidolic Acid,Pyroglutamic Acid,5-Ketoproline,5-Oxopyrrolidine-2-Carboxylic Acid,Magnesium Pidolate,Pyroglutamate,Pidolate, Magnesium
D003106 Colon The segment of LARGE INTESTINE between the CECUM and the RECTUM. It includes the ASCENDING COLON; the TRANSVERSE COLON; the DESCENDING COLON; and the SIGMOID COLON. Appendix Epiploica,Taenia Coli,Omental Appendices,Omental Appendix,Appendices, Omental,Appendix, Omental
D005973 Glutamine A non-essential amino acid present abundantly throughout the body and is involved in many metabolic processes. It is synthesized from GLUTAMIC ACID and AMMONIA. It is the principal carrier of NITROGEN in the body and is an important energy source for many cells. D-Glutamine,L-Glutamine,D Glutamine,L Glutamine
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
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

Related Publications

K Karagiannis, and A Manolopoulou, and G Stavropoulos, and C Poulos, and C C Jordan, and R M Hagan
August 1987, Journal of medicinal chemistry,
K Karagiannis, and A Manolopoulou, and G Stavropoulos, and C Poulos, and C C Jordan, and R M Hagan
November 1992, International journal of peptide and protein research,
K Karagiannis, and A Manolopoulou, and G Stavropoulos, and C Poulos, and C C Jordan, and R M Hagan
July 1986, Journal of medicinal chemistry,
K Karagiannis, and A Manolopoulou, and G Stavropoulos, and C Poulos, and C C Jordan, and R M Hagan
June 1987, Biochemical and biophysical research communications,
K Karagiannis, and A Manolopoulou, and G Stavropoulos, and C Poulos, and C C Jordan, and R M Hagan
March 1991, International journal of peptide and protein research,
K Karagiannis, and A Manolopoulou, and G Stavropoulos, and C Poulos, and C C Jordan, and R M Hagan
September 1993, Journal of medicinal chemistry,
K Karagiannis, and A Manolopoulou, and G Stavropoulos, and C Poulos, and C C Jordan, and R M Hagan
July 1994, Neuropeptides,
K Karagiannis, and A Manolopoulou, and G Stavropoulos, and C Poulos, and C C Jordan, and R M Hagan
March 1983, International journal of peptide and protein research,
K Karagiannis, and A Manolopoulou, and G Stavropoulos, and C Poulos, and C C Jordan, and R M Hagan
June 1995, International journal of peptide and protein research,
K Karagiannis, and A Manolopoulou, and G Stavropoulos, and C Poulos, and C C Jordan, and R M Hagan
July 2010, Peptides,
Copied contents to your clipboard!