Biological activity of silylated amino acid containing substance P analogues.
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.
Cavelier
F
F
Laboratoire des Aminoacides, Peptides et Protéines, UMR-CNRS 5810, Universités Montpellier I et II, UM II - CC19, 34095 Montpellier cedex 05, France. florine@univ-montp2.fr
Marchand
D
D
Martinez
J
J
Sagan
S
S
D000262:Adenylyl Cyclases / Q000378:metabolism; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D001681:Biological Assay; D016466:CHO Cells; D006224:Cricetinae; D005998:Glycine / Q000737:chemistry; D017646:Organosilicon Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011392:Proline / Q000031:analogs & derivatives* / Q000737:chemistry; D018040:Receptors, Neurokinin-1 / Q000819:agonists / Q000378:metabolism; D013373:Substance P / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D014297:Trimethylsilyl Compounds / Q000737:chemistry; D010738:Type C Phospholipases / Q000378:metabolism
D017646:Organosilicon Compounds; D018040:Receptors, Neurokinin-1; D014297:Trimethylsilyl Compounds; C455420:silaproline; D013373:Substance P; D011392:Proline; D010738:Type C Phospholipases; D007703:Peptidyl-Dipeptidase A; D000262:Adenylyl Cyclases; D005998:Glycine