80852-33-1Relevant academic research and scientific papers
Synthesis of bioorthogonal and crosslinking amino acids for use in peptide synthesis
Sundaram,Morgan, Ian R.,Tippmann, Eric M.
scheme or table, p. 1381 - 1384 (2011/09/15)
The ability to incorporate non-canonical amino acids into proteins by genetic or chemical methods allows one to introduce novel chemical properties into a protein at a defined residue. Such a residue may then be modified using common organic transformations. In this way, the structure or function of the peptide may be altered without perturbing any of the other neighbouring amino acids in the peptide chain. Here, we describe the syntheses and potential applications of multiple para-substituted phenylalanine derivatives comprising an isothiocyanate, α-diazoketone, or nitrone functionality. In all, three novel amino acids were synthesized in good overall yields. These non-canonical amino acids permit the further development of in vitro and in vivo chemoselective and regioselective bioconjugate reactions not possible with other reagents.
Differences in backbone structure between angiotensin II agonists and type I antagonists
Matsoukas,Agelis,Wahhab,Hondrelis,Panagiotopoulos,Yamdagni,Wu,Mavromoustakos,Maia,Ganter,Moore
, p. 4660 - 4669 (2007/10/02)
Type I angiotensin II antagonists with O-methyl-L-homoserine [HSer(γ- OMe)] and δ-methoxy-L-norvaline [Nva(δ-OMe)] at position 8 have been prepared by the solid-phase method, purified by reverse-phase HPLC, and bioassayed in the rat uterus, and their backbone conformational properties were investigated by nuclear Overhauser effect (NOE) spectroscopy. [Sar1,HSer-(γ-OMe)8]ANGII, [HSer(γ-OMe)8]ANGII, [Des1,HSer(γ- OMe)8]ANGII, [Sar1,Nva(δ-OMe)8]-ANGII, and [Des1,Nva(δ-OMe)8]ANGII had, respectively, the following antagonist activities, pA2: 7.6, 7.5, 1]ANGII with δ-hydroxy-L-norvaline [Nva(δ- OH)], δ-methoxy-L-norvaline [Nva(δ-OMe)], 4'-carboxyphenylalanine [Phe(4'- COOH)], and 4'-(trifluoromethyl)phenylalanine [Phe(4'-CF3)] at position 4 were also prepared by solid phase and bioassayed in the rat uterus. [Sar1,Nva(δ-OH)4]ANGII, [Aib1,Nva(δ-OMe)4]ANGII, [Sar1, DL-Phe(4'- COOH)4]ANGII, and [Sar1,DL-Phe(4'-CF3)4]ANGII had, respectively, agonist activities as follows: 4%, 1.5%, 3%, 8 in Sarilesin with the higher homologs HSer(γ-OMe) and Nva(δ-OMe) does not greatly alter the structural requirements necessary for expression of type I antagonist activity, while replacement of the tyrosine hydroxyl in [Sar1]ANGII by the carboxylate or the trifluoromethyl group abolishes activity, suggesting that the tyrosinate pharmacophore cannot be replaced by any negatively charged or electronegative group. Conformational investigation of the ANGII type I antagonists [HSer(γ- OMe)8]ANGII and [Sar1 Nva(δ-OMe)8]ANGII in DMSO by 1D-NOE spectroscopy revealed that the Tyr-Ile-His bend, a conformational property found in ANGII and [Sar1]ANGII (J. Biol. Chem. 1994, 269, 5303) is not present in type I antagonists, providing for the first time an important conformational difference between angiotensin II agonists and type I antagonists.
Investigation of the active site of aminopeptidase A using a series of new thiol-containing inhibitors
Chauvel,Coric,Llorens-Cortes,Wilk,Roques,Fournie- Zaluski
, p. 1339 - 1346 (2007/10/02)
Aminopeptidase A (APA) and aminopeptidase N (APN) are two metallopeptidases which have been suggested to be involved in the enzymatic cascade of the renin-angiotensin system. APA liberates angotensin III from angiotensin II by releasing the N-terminal asp
