Aspartic acid, ionic forms

Hydrophobic interaction chromatography (HIC) can be considered to be a variant of reversed phase chromatography, in which the polarity of the mobile phase is modulated by adjusting the concentration of a salt such as ammonium sulfate. The analyte, which is initially adsorbed to a hydrophobic phase, desorbs as the ionic strength is decreased. One application demonstrating extraordinary selectivity was the separation of isoforms of a monoclonal antibody differing only in the inclusion of a particular aspartic acid residue in the normal, cyclic, or iso forms.27 The uses and limitations of hydrophobic interaction chromatography in process-scale purifications are discussed in Chapter 3. 

Molecules of nitrogen-containing compounds, such as alkaloids, amines, and peptides, usually contain (under physiological conditions) positively charged N-atoms that can form ionic bonds with negatively charged amino acid residues of glutamic and aspartic acid in proteins. Both the covalent and the noncovalent interactions will modulate the three-dimensional protein structure, that is, the conformation that is so important for the bioactivities of proteins (enzymes. 

An ionic bond can be formed between the carboxylate ion of an acidic residue such as aspartic acid and the ammonium ion of a basic residue such as lysine (Fig. 3.9). 

Recently, Liardon and Hurrell (1983) reported D-serine measurements which indicate that serine is indeeed racemizing about twice as fast as aspartic acid, thus verifying our earlier predictions. This rate relationship should be. true only in base-catalyzed racemization, however, because the COO (delta-carboxylate) ionic species of the carboxylic acid side chain is the predominant racemizing form under alkaline conditions. 

Poly(aspartic acid) (PAA) is an ionic polymer that shows water solubility, which has been found to undergo lysosomal biodegradation. Due to the high functionality of the polymer, many block copolymers and chemically modified forms of PAA are synthesized with aspartic acid and other synthetic biodegradable polymeric moieties that form drug delivery vehicles with core-forming micellar nanostructures, and are currently xmder late stage clinical trials [39]. 

Ionic bonds can form between the positively and negatively charged R groups of acidic and basic amino acids. For example, an ionic bond can form between the —NH3 in the R group of lysine and the —COO of aspartic acid. 

A technique used to obtain spherical particles is the spray-drying technique. The spray-drying method has reportedly provided small-size, protein-loaded chitosan-alginate microparticles with appropriate protein immobilization capacity [98]. It has been applied to BSA/sodium alginate/chitosan solutions to obtain microparticles [98]. Moreover, chitosan nanoparticles can be obtained by ionic crosslinking method. It has produced nanoparticles based on ionic gelation process of tripolyphosphate (TPP) and chitosan [99]. Nevertheless, another physical method called layer-by-layer can be used to form chitosan particles. Through the layer-by-layer technique submicron (40 nm) capsules with poly(L-aspartic acid) and chitosan for transmucosal delivery of proteins and peptides have been obtained [100]. 

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