Synthesis, purification and biological activity of (Ser10-phosphatidyl)-urodilatin (phosphourodilatin).
H Mostafavi, K Adermann, S Austermann, M Raida, M Meyer, W G Forssmann
文献索引:Biomed. Pept. Proteins Nucleic Acids 1(5) , 255-60, (1995)
全文:HTML全文
摘要
Based on the global phosphorylation approach, a selective synthesis of (Ser10-phosphatidyl)-urodilatin (phosphourodilatin), which contains 32 amino acid residues and a disulfide loop is described. The peptide was assembled stepwise on a polyethyleneglycol-polystyrene support using Fmoc-chemistry. The phosphorylation was performed on-resin by phosphitylation with a large excess of di-tert-butyl-N,N-diethylphosphoramidite within 1 hour, followed by oxidation with tert-butylhydroperoxide to the protected phosphopeptide. After cleavage and deprotection the disulfide bridge was introduced without side reactions by iodine titration of the mono-acetamidomethyl protected crude peptide. During the synthetic pathway, the acylation with side chain-unprotected Fmoc-serine and the phosphitylation satisfactorily yielded the expected intermediates. In some phosphorylation experiments a by-product having a reduced mass corresponding to the H-phosphonate was observed. Illustrated with the synthesis of phosphourodilatin, this type of by-product, which could not be separated by HPLC, and the difficult amino acid sequence make the synthesis of a large phosphopeptide a more delicate task than the synthesis of short phosphopeptides, which do not contain oxidation-sensitive amino acids, difficult sequences or additional structural elements such as disulfide loops. The biological activity of phosphourodilatin was compared with non-phosphorylated urodilatin in two assay systems. Both peptides revealed a vasorelaxant effect on aortic smooth muscle strips and induced a cGMP-generation in RFL-6 cells with increasing dose dependency.
相关化合物
相关文献:
Calcium phosphate nanoparticles: colloidally stabilized and made fluorescent by a phosphate-functionalized porphyrin. Ganesan K, et al.
[J. Mater. Chem. 18(31) , 3655-61, (2008)]
1996-02-01
[Bioorg. Med. Chem. 4(2) , 143-50, (1996)]
1996-01-05
[J. Biol. Chem. 271(1) , 168-73, (1996)]