Intramolecularly quenched fluorogenic peptide substrates for human renin

✍ Scribed by Maria C.F. Oliveira; Izaura Y. Hirata; Jair R. Chagas; Paulo Boschcov; Roseli A.S. Gomes; Amintas F.S. Figueiredo; Luiz Juliano

• Publisher: Elsevier Science
• Year: 1992
• Tongue: English
• Weight: 591 KB
• Volume: 203
• Category: Article
• ISSN: 0003-2697
• DOI: 10.1016/0003-2697(92)90040-e

✦ Synopsis

Six intramolecularly quenched fluorogenic peptides related to the sequences Phe8 to His13, His6 to His13, and Tyr4 to His13 of the human angiotensinogen, containing o-aminobenzoyl (Abz) and ethylenediamine dinitrophenyl (EDDnp) groups at amino- and carboxyl-terminal amino acids residues, were synthesized by classical solution methods. The Leu-Val is the only bond of all obtained peptides that was hydrolyzed by human renin with different degrees of purity and was resistant to hydrolysis by pig renin and cathepsin D. The hydrolysis of Abz-His-Pro-Phe-His-Leu-Val-Ile-His-EDDnp by human renin was inhibited by a highly specific transition-state analog of angiotensinogen (IC50 = 7.8 x 10(-9) M), described by K. Iizuka et al. (1990, J. Med. Chem. 33, 2707-2714). Therefore, specific and sensitive substrates for the continuous assay of human renin in which as little as 70 microGU of human renin could be detected by Abz-Phe-His-Leu-Val-Ile-His-EDDnp were described. The optimal pHs of hydrolysis of the substrates were in the range 4 to 6.