Abstract
Apelin is an important mammalian peptide hormone with a range of physiological roles, especially in the cardiovascular system. The apelinergic system is a promising target for treatment of disease, but this remains to be realized due to rapid proteolysis of apelin-derived peptides by proteases, including neprilysin (NEP). The synthetic analogues modified within the NEP degradation site ("RPRL" motif) showed improved in vitro proteolytic stability while maintaining receptor-binding affinities, with three candidate peptides retaining full cardiovascular activities for potential therapeutic application. Many such analogues proved physiologically inactive even with relatively conservative modifications, highlighting the importance of this region for full agonist activity of this peptide hormone.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apelin Receptors
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Blood Pressure / drug effects
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CHO Cells
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Cardiovascular Agents / blood
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Cardiovascular Agents / chemical synthesis*
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Cardiovascular Agents / pharmacology
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Cricetulus
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Heart Rate / drug effects
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Humans
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Intercellular Signaling Peptides and Proteins / blood
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Intercellular Signaling Peptides and Proteins / chemical synthesis*
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Intercellular Signaling Peptides and Proteins / pharmacology
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Mice
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Neprilysin / blood*
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Protein Isoforms / blood
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Protein Isoforms / chemical synthesis
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Protein Isoforms / pharmacology
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Rats
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Receptors, G-Protein-Coupled / metabolism
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Apelin Receptors
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Aplnr protein, rat
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Cardiovascular Agents
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Intercellular Signaling Peptides and Proteins
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Protein Isoforms
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Receptors, G-Protein-Coupled
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apelin 13, Pyr(1)-
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apelin 17 peptide, human
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apelin-13 peptide
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Neprilysin