Aspartic acid peptides hydrolysis

Asparagine residues in peptides and proteins undergo deamidation via cyclic imide formation followed by subsequent hydrolysis to form the corresponding aspartic and Ao-aspartic acid peptides. This mechanism occurs primarily under neutral-to-basic pH conditions. Deamidation of an asparagine residue to the corresponding aspartic acid residue may also occur via a mechanism that does not involve cyclic imide formation, as shown in Scheme 80. Glutamine residues also undergo deamidation, but at much slower rates. 

Peptides and proteins having an aspartic acid residue undergo hydrolysis, isomerization, and racemization via cyclic imide formation. As shown in Scheme 80, L-aspartic acid peptide can isomerize to L-iso -aspartic acid peptide via its L-cyclic imide. The L-cyclic imide intermediate is capable of undergoing racemization to the D-cyclic imide and thus forms the D-aspartic acid peptide and the D-Ao-aspartic acid peptide on hydrolysis. 

Aspaityl proteinases are proteinases that utilize the terminal carboxyl moiety of the side chain of aspartic acid to effect peptide bond hydrolysis. 

Another competing cyclisation during peptide synthesis is the formation of aspartimides from aspartic acid residues [15]. This problem is common with the aspartic acid-glycine sequence in the peptide backbone and can take place under both acidic and basic conditions (Fig. 9). In the acid-catalysed aspartimide formation, subsequent hydrolysis of the imide-containing peptide leads to a mixture of the desired peptide and a (3-peptide. The side-chain carboxyl group of this (3-peptide will become a part of the new peptide backbone. In the base-catalysed aspartimide formation, the presence of piperidine used during Fmoc group deprotection results in the formation of peptide piperidines. 

Moser et al. (1968) (one of the co-authors was Clifford Matthews) reported a peptide synthesis using the HCN trimer aminomalonitrile, after pre-treatment in the form of a mild hydrolysis. IR spectra showed the typical nitrile bands (2,200 cm ) and imino-keto bands (1,650 cm ). Acid hydrolysis gave only glycine, while alkaline cleavage of the polymer afforded other amino acids, such as arginine, aspartic acid, threonine etc. The formation of the polymer could have occurred according to the scheme shown in Fig. 4.9. 

At this point, you can deduce two possible sequences for Q.) (5) Trypsin hydrolysis of L gives a peptide of composition Ala, Asp, Phe which, with 2,4-dinitrofluorobenzene, gives the 2,4-dinitrophenyl derivative of aspartic acid. (6) Partial acid hydrolysis of eledoisin gives several dipeptides, among them Ser-Lys and Pro-Ser. 

The amide bonds in peptides and proteins can be hydrolyzed in strong acid or base Treatment of a peptide or protein under either of these conditions yields a mixture of the constituent amino acids. Neither acid- nor base-catalyzed hydrolysis of a protein leads to ideal results because both tend to destroy some constituent ammo acids. Acid-catalyzed hydrolysis destroys tryptophan and cysteine, causes some loss of serine and threonine, and converts asparagine and glutamine to aspartic acid and glutamic acid, respectively. Base-catalyzed hydrolysis leads to destruction of serine, threonine, cysteine, and cystine and also results in racemization of the free amino acids. Because acid-catalyzed hydrolysis is less destructive, it is often the method of choice. The hydrolysis procedure consists of dissolving the protein sample in aqueous acid, usually 6 M HC1, and heating the solution in a sealed, evacuated vial at 100°C for 12 to 24 hours. 

Aspartame. Aspartame is a widely used intense sweetener that has excellent taste characteristics, ft is a peptide made from two amino acids, phenylalanine and aspartic acid, but will in an acidic beverage medium slowly hydrolyse to its components. The fact that aspartame is a source of phenylalanine is of concern to consumers with certain complaints, and suitable label declarations are now required by law. Technically, this slow hydrolysis brings about loss of sweetness. 

From a rare fungus you have isolated an octapeptide that prevents baldness, and you wish to determine the peptide sequence. The amino acid composition is Lys(2), Asp, Tyr, Phe, Gly, Ser, Ala. Reaction of the intact peptide with FDNB yields DNP-alanine plus 2 moles of e-DNP-lysine on acid hydrolysis. Cleavage with trypsin yields peptides the compositions of which are (Lys, Ala, Ser) and (Gly, Phe, Lys), plus a dipeptide. Reaction with chymotrypsin releases free aspartic acid, a tetrapeptide with the composition (Lys, Ser, Phe, Ala), and a tripeptide the composition of which, following acid hydrolysis, is (Gly, Lys, Tyr). What is the sequence ... 

In a classic study on bovine pancreatic ribonuclease A at 90°C and pH conditions relevant for catalysis, irreversible deactivation behavior was found to be a function of pH (Zale, 1986) at pH 4, enzyme inactivation is caused mainly by hydrolysis of peptide bonds at aspartic acid residues as well as deamidation of asparagine and/or glutamine residues, whereas at pH 6-8, enzyme inactivation is caused mainly by thiol-disulfide interchange but also by fi-elimination of cystine residues, and deamidation of asparagine and/or glutamine residues. 

Hydrolysis. Peptide bonds of aspartic acid (Asp) residues are cleaved under dilute acidic conditions. Hydrolysis can take place at the N-terminal, the C-terminal, or both terminal peptide bonds adjacent to the Asp residue. 

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