119363-63-2Relevant articles and documents
Topographic Probes of Angiotensin and Receptor: Potent Angiotensin II Agonist Containing Diphenylalanine and Long-Acting Antagonists Containing Biphenylalanine and 2-Indan Amino Acid in Position 8
Hsieh, Kun-hwa,LaHann, Thomas R.,Speth, Robert C.
, p. 898 - 903 (1989)
A series of phenylalanine-mimicking amino acids with increasing conformational restraint were prepared and incorporated into angiotensin II, in order to develop topographic probes of angiotensin useful for probing receptor boundaries by molecular graphics
Synthesis and biological activity of ketomethylene pseudopeptide analogues as thrombin inhibitors
Cheng,Goodwin,Schully,Kakkar,Claeson
, p. 3364 - 3369 (2007/10/02)
Ketomethylene pseudopeptide analogues Aa-Pro-Argψ(COCH2)Gly-pip, 1, where Aa are D- or L-amino acids (Dpa, β,β-diphenylalanine; αNal, α- naphthylalanine; βNal, β-naphthylalanine; Fgl, fluorenylglycine) with highly lipophilic side chains and ψ(COCH2) is a ketomethylene pseudopeptide bond, have been synthesized through a modified Dakin-West reaction under very mild conditions with a high yield using tripeptide 4 with a labile functional group directly on the side chain. Their enzymatic assay of thrombin inhibition has been carried out. The structure-activity relationship study indicated that a lipophilic side chain on the amino acid in the P3 position is very important for binding to the apolar site of thrombin. Compound 1a with D-Dpa at the P3 position has a K(i) of 0.2 μM and it doubles thrombin clotting time at only 3 times higher concentration. These values are about 7 times better than those of the corresponding D-Phe analogues. Furthermore, 1a shows poor inhibitory activity against plasmin, factor Xa, urokinase, and kallikrein. Preliminary in vivo testing (3-4-kg rabbit as the animal model) shows no observable side effect (change of blood pressure and accumulation of blood platelet in lungs) at a dose of 1 mg/kg.
