Abstract
The need to replace natural amino acids in peptides with nonproteinogenic counterparts to obtain new medicinal agents has stimulated a great deal of innovation on synthetic methods. Here, we report the incorporation of non-natural silylated amino acids in substance P (SP), the binding affinity for the two hNK-1 binding sites and, the potency to stimulate phospholipase C (PLC) and adenylate cyclase of the resulting peptide. We also assess the improvement of their stability towards enzyme degradation. Altogether, we found that replacing glycine with silaproline (Sip) in position 9 of SP leads to a potent analogue exhibiting an increased resistance to angiotensin-converting enzyme hydrolysis.
MeSH terms
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Adenylyl Cyclases / metabolism
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Amino Acid Substitution
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Animals
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Binding Sites
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Biological Assay
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CHO Cells
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Cricetinae
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Glycine / chemistry
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Organosilicon Compounds / chemistry*
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Organosilicon Compounds / metabolism
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Organosilicon Compounds / pharmacology*
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Peptidyl-Dipeptidase A / metabolism
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Proline / analogs & derivatives*
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Proline / chemistry
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Receptors, Neurokinin-1 / agonists
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Receptors, Neurokinin-1 / metabolism
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Substance P / analogs & derivatives*
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Substance P / chemical synthesis
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Substance P / metabolism
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Trimethylsilyl Compounds / chemistry
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Type C Phospholipases / metabolism
Substances
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Organosilicon Compounds
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Receptors, Neurokinin-1
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Trimethylsilyl Compounds
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silaproline
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Substance P
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Proline
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Type C Phospholipases
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Peptidyl-Dipeptidase A
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Adenylyl Cyclases
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Glycine