1.Resolution of DL-2-aminosuberic acid via protease-catalyzed ester hydrolysis.
Rivard M1, Malon P, Cerovský V. Amino Acids. 1998;15(4):389-92.
Papain-catalyzed regioselective cleavage of alpha-methyl ester in Z-DL-Asu(OMe)-OMe leads to Z-L-Asu(OMe)-OH and Z-D-Asu(OMe)-OMe. Subsequent saponifications yield Z-L-Asu-OH and Z-D-Asu-OH. The enzymatic alpha-ester hydrolysis was also achieved by subtilisin BPN' in organic solvent with low water content.
2.A simple route to [11C]N-Me labeling of aminosuberic acid for proof of feasibility imaging of the x(C)⁻ transporter.
Yang H1, Miao Q1, Johnson BF2, Rishel MJ2, Sossi V3, Dinelle K3, Bénard F4, Yapp DT5, Webster JM2, Schaffer P6. Bioorg Med Chem Lett. 2014 Dec 1;24(23):5512-5. doi: 10.1016/j.bmcl.2014.10.004. Epub 2014 Oct 13.
Oxidative stress has been implicated in a variety of conditions, including cancer, heart failure, diabetes, neurodegeneration and other diseases. A potential biomarker for oxidative stress is the cystine/glutamate transporter, system x(C)(-). L-Aminosuberic acid (L-ASu) has been identified as a system x(C)(-) substrate. Here we report a facile method for [(11)C]N-Me labeling of L-ASu, automation of the radiochemical process, and preliminary PET imaging with EL4 tumor bearing mice. The results demonstrate uptake in the tumor above background, warranting further studies on the use of radiolabeled analogs of L-ASu as a PET imaging agent for system x(C)(-).
3.Probing the structure-activity relationship of endogenous histone deacetylase complexes with immobilized peptide-inhibitors.
Sindlinger J1, Bierlmeier J1, Geiger LC1, Kramer K2, Finkemeier I2,3, Schwarzer D1. J Pept Sci. 2016 Apr 12. doi: 10.1002/psc.2875. [Epub ahead of print]
Histone deacetylases (HDACs) are key regulators of numerous cellular proteins by removing acetylation marks from modified lysine residues. Peptide-based HDAC probes containing α-aminosuberic acid ω-hydroxamate have been established as useful tools for investigating substrate selectivity and composition of endogenous HDAC complexes in cellular lysates. Here we report a structure-activity study of potential HDAC-probes containing derivatives of the hydroxamate moieties. While most of these probes did not recruit significant amounts of endogenous HDACs from cellular lysates, peptides containing Nε-acetyl-Nε-hydroxy-L-lysine served as HDAC probe. The recruitment efficiency varied between HDACs and was generally lower than that of α-aminosuberic acid ω-hydroxamate probes, but showed a similar global interaction profile. These findings indicate that Nε-acetyl-Nε-hydroxy-L-lysine might be a useful tool for investigations on HDAC complexes and the development of HDAC inhibitors.
4.Tandem enzymatic resolution yielding L-alpha-aminoalkanedioic acid omega-esters.
Nishino N1, Arai T, Ueno Y, Ohba M. Chem Pharm Bull (Tokyo). 1996 Jan;44(1):212-4.
The tandem action of serine protease (alpha-chymotrypsin or subtilisin BPN') and Aspergillus genus aminoacylase on racemic N-acetyl-alpha-aminoalkanedioic acid alpha,omega-diester produced L-alpha-aminoalkanedioic acid omega-ester in good yield and high optical purity. L-alpha-Aminosuberic acid omega-ester thus obtained was conveniently introduced into an oxytocin analog, [Asu1,6]oxytocin, by the solid-phase-synthesis and cyclization-cleavage method with oxime resin.