- DERIVATIVES COMPRISING AN APELIN ANALOGUE AND USES THEREOF
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The present invention relates to derivatives comprising an apelin analogue; wherein the apelin analogue comprises two amino acids having a sulphur atom in the side chain, wherein said two amino acids are covalently linked via a methylene bridge. The invention also relates to the pharmaceutical use of the derivatives, preferably in the treatment of all forms of cardiovascular disease.
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Page/Page column 33-35; 39
(2019/12/25)
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- Identifying structural determinants of potency for analogs of apelin-13: Integration of C-terminal truncation with structure-activity
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Apelin peptides function as endogenous ligands of the APJ receptor and have been implicated in a number of important biological processes. While several apelinergic peptides have been reported, apelin-13 (Glu-Arg-Pro-Arg-Leu-Ser-His- Lys-Gly-Pro-Met-Pro-Phe) remains the most commonly studied and reported ligand of APJ. This study examines the effect of C-terminal peptide truncations and comprehensive structure-activity relationship (SAR) for a series of analogs based on apelin-13 in an attempt to develop more potent and stable analogs. C-terminal truncation studies identified apelin-13 (N-acetyl 2-11) amide (9) as a potent agonist (EC50 = 4.4 nM). Comprehensive SAR studies also determined that Arg-2, Leu-5, Lys-8, Met-11, were key positions for determining agonist potency, whereas the hydrophobic volume of Lys-8 was a specific determinate of activity. Plasma stability studies on the truncated 10-mer peptide 28 (EC50 = 33 nM) indicated the primary sites of cleavage occurred between Nle-3 and Leu-4 and also between Ala-5 and Ala-6. These new ligands represent the shortest known apelin peptides with good functional potency.
- Zhang, Yanyan,Maitra, Rangan,Harris, Danni L.,Dhungana, Suraj,Snyder, Rodney,Runyon, Scott P.
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p. 2992 - 2997
(2014/05/20)
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