128135-48-8Relevant academic research and scientific papers
Reactivity of dehydroaspartic acid derivatives under peptide coupling conditions
Subasinghe,Johnson
, p. 2649 - 2652 (2007/10/02)
The reactivity of α-carboxy-activated dehydroaspartic acid derivatives with various N- and O-nucleophiles is described for the first time. Reaction of amino acid derivatives with Ac-Δ(Z)Asp(OBu(t))-OH (4a) under a variety of coupling conditions gave very poor yields of the resulting dehydroaspartyl dipeptides, while the coupling of 4a with oxygen nucleophiles gave very good yields of the dehydroaspartyl esters. In contrast, the coupling of amino acids with Cbz-Δ(Z)Asp(Obu(t))-OH (4b) gave good yields of dehydroaspartyl dipeptides. The formation of a highly reactive oxazolone intermediate is proposed to explain the low yields of peptide coupling between 4a and amino acids.
Synthesis of acyclic and dehydroaspartic acid analogues of Ac-Asp-Glu-OH and their inhibition of rat brain N-acetylated α-linked acidic dipeptidase (NAALA dipeptidase)
Subasinghe,Schulte,Chan,Roon,Koerner,Johnson
, p. 2734 - 2744 (2007/10/02)
The following structural and conformationally constrained analogues of Ac-Asp-Glu-OH (1) were synthesized: Ac-Glu-Glu-OH (2), Ac-D-Asp-Glu-OH (3), Ac-Glu-Asp-OH (4), Ac-Asp-Asp-OH (5), Ac-Asp-3-aminohexanedioic acid (6), Ac-3-amino-3-(carboxymethyl)propanoyl-Glu-OH (7), N-succinyl-Glu-OH (8), N-maleyl-Glu-OH (9), N-fumaryl-Glu-OH (10), and Ac-Δ(z)Asp-Glu-OH (11). These analogues were evaluated for their ability to inhibit the hydrolysis of Ac-Asp-[3,4-3H]-Glu-OH by N-acetylated α-linked acidic dipeptidase (NAALA dipeptidase) in order to gain some insight into the structural requirements for the inhibition of this enzyme. Analogues 4-6 and 9 were very weak inhibitors of NAALA dipeptidase (K(i) > 40 μM), while 2, 3, and 7 with K(i) values ranging from 3.2-8.5 μM showed intermediate inhibitory activity. The most active inhibitors of NAALA dipeptidase were compounds 8, 10, and 11 with K(i) values of 0.9, 0.4, and 1.4 μM, respectively. These results suggest that the relative spacing between the side chain carboxyl and the α-carboxyl group of the C-terminal residue may be important for binding to the active site of the enzyme. They also indicate that the χ1 torsional angle for the aspartyl residue is in the vicinity of 0°.
