Aspartic acid discovery

Before analyzing in detail the conformational behaviour of y9-peptides, it is instructive to look back into the origins and the context of this discovery. The possi-bihty that a peptide chain consisting exclusively of y9-amino acid residues may adopt a defined secondary structure was raised in a long series of studies which began some 40 years ago, on y9-amino acid homopolymers (nylon-3 type polymers), such as poly(/9-alanine) 3 [14, 15], poly(y9-aminobutanoic acid) 4 [16-18], poly(a-dialkyl-/9-aminopropanoic acid) 5 ]19], poly(y9-L-aspartic acid) 6 ]20, 21], and poly-(a-alkyl-/9-L-aspartate) 7 [22-36] (Fig. 2.1). 

The discovery of homochirality on a planet such as Mars could be an excellent biomarker and strengthen the argument for life on Mars. With an EE in the solar nebula there should be an EE on the surface of Mars of order 9 per cent but remains of ancient life on Mars would show a greater excess. The interchange of enantiomers occurs naturally in a process called racemisation and for the most labile amino acid, aspartic acid, the half-life for the racemisation is 800 years at 300 K in 800 years, half of the non-biotic aspartic acid would racemise and the EE would go to zero. In dry conditions, however, the half-life is much longer, perhaps as large as 5 x 104 years at 300 K. Extrapolation of the racemisation rate to 215 K, the equatorial temperature of Mars, extends the half-life further to 3 x 1012 years and to 1027 years at 150 K, Martian polar temperatures. Hence, discovery of a considerable EE in the Martian soil would be a strong indicator of ancient Martian life. 

Historically, L-aspartic acid was produced by hydrolysis of asparagine, by isolation from protein hydrolysates, or by the resolution of chemically synthesized d,L-aspartate. With the discovery of aspartase (L-aspartate ammonia lyase, EC 4.3.1.1),57 fermentation routes to L-aspartic acid quickly superseded the initial chemical methods. These processes are far more cost effective than the fermentation routes, and aspartate is now made exclusively by enzymatic methods that use variations of the general approach outlined in Scheme 2.19.53-57-65... 

Keywords Alzheimer s disease- Aspartic acid protease- BACE-1- Fragment-based drug discovery- Structure-based design... 

Lichtor PA, Miller SJ (2011) One-bead-one-catalyst approach to aspartic acid-based oxidation catalyst discovery. ACS Comb Sci 13 321-326... 

Aspartate transcarbamylase (ATCase) catalyzes the formation of carbamoyl aspartate with CP and aspartic acid as substrates. It is the first specific enzyme for the pyrimidine pathway, and it holds a special place in the historical development of end-product control at this level. The concept of feedback inhibition as an important regulatory mechanism evolved from the initial discovery by Yates and Pardee [90] that CTP is a potent inhibitor of ATCase. It has since developed into a prototype for a regulatory protein with classic allosteric properties. A thorough characterization of the enzyme and its properties has been made through the combined efforts of Gerhart, Pardee, Schachman, and Changeux [91-97]. A summary of these studies follows. 

The carboxyl proteases are so called because they have two catalytically essential aspartate residues. They were formerly called acid proteases because most of them are active at low pH. The best-known member of the family is pepsin, which has the distinction of being the first enzyme to be named (in 1825, by T. Schwann). Other members are chymosin (rennin) cathepsin D Rhizopus-pepsin (from Rhizopus chinensis) penicillinopepsin (from Penicillium janthinel-lum) the enzyme from Endothia parasitica and renin, which is involved in the regulation of blood pressure. These constitute a homologous family, and all have an Mr of about 35 000. The aspartyl proteases have been thrown into prominence by the discovery of a retroviral subfamily, including one from HIV that is the target of therapy for AIDS. These are homodimers of subunits of about 100 residues.156,157 All the aspartyl proteases contain the two essential aspartyl residues. Their reaction mechanism is the most obscure of all the proteases, and there are no simple chemical models for guidance. 

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