125907-76-8Relevant academic research and scientific papers
Potent renin inhibitory peptides containing hydrophilic end groups
Bundy,Pals,Lawson,Couch,Lipton,Mauragis
, p. 2276 - 2283 (1990)
A previously reported renin inhibitor, Boc-Pro-Phe-N(Me)His-Leuψ[CHOHCH2]Val-Ile-Amp (U-71038), was altered by the incorporation of polar, hydrophilic moieties at either end, e.g., tris(hydroxymethyl)aminomethane (THAM) or glucosamine urea groups at the N-terminus, and the THAM amide or aminomethylpyridine N-oxide at the C-terminus. These modified analogues, with dramatically improved water solubility, all retained the potent renin inhibitory activity of U-71038 in vitro. The fact that good activity was maintained in these new analogues, which possess hydrophilicity and steric bulk considerably different from the parent compound, suggests that neither end of these molecules is critical for recognition and binding of the inhibitors by renin. These modified analogues were evaluated in a rat model, and several exhibited hypotensive activity after both oral and iv administration which was greater in magnitude and longer in duration than that caused by equimolar doses of U-71038. Furthermore, unlike U-71038, the oral activity of these analogues was not dependent upon administration in a citric acid vehicle.
Renin inhibiting peptides with polar end groups
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, (2008/06/13)
The present invention provides novel renin-inhibiting peptides having a noncleavable transition state insert corresponding to the 10,11- position of the renin substrate (angiotensinogen) and a polyhydroxy-substituted alkyl moiety bonded directly through carbon or nitrogen to the N-terminus. Such inhibitors are useful for the diagnosis and control of renin-dependent hypertension and other related diseases.
