Side-chain carboxyl groups, acidity

A side chain carboxyl group in perhydropyrido[l,2-a]pyrazines was obtained from an ester group by acidic or alkalic hydrolysis. A side chain carboxyl group was converted into a carboxamide group by the treatment with an amine in the presence of 1-hydroxybenzotriazole (OOJAP(K)OO/ 86659). 

The side-chain carboxylate group of an aspartic acid acts as a base and removes an acidic a proton from acetyl CoA, while the N-H group on the side chain of a histidine acts as an acid and donates a proton to the car bonyl oxygen, giving an enol. 

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. 

HPMA [36] and a vinyl metal-chelating monomer A-(A/, A/ -dicarboxy-methylaminopropyl)methacrylamide synthesized [35]. Chemical structures of HPMA and DAMA are given in Figure 4. Poly(HPMA-co-DAMA) was prepared by free radical copolymerization in methanol with AIBN as initiator. Molecular weight distribution was determined by size exclusion chromatography and content of side-chain carboxylic group by acid-base titration. 

Aspartic acid has a side chain carboxyl group that will lose a proton and become an anionic carboxylate group under physiological conditions. Aspartic acid is the metabolic precursor to gamma (y)-aminobutyric acid (GABA), an important inhibitory neurotransmitter in the human central nervous system. 

Fig. 6.21. In situ activation of a carboxylic acid—i.e., the side chain carboxyl group of protected L-aspartic acid—as the mixed anhydride (B) and its aminolysis to a Weinreb amide. How this Weinreb amide acylates an organolithium compound is shown in Figure 6.44. The acylation of an H nucleophile by a second Weinreb amide is presented in Figure 6.42 and the acylation of a di(ketone enolate) by a third Weinreb amide in Figure 13.64. Figure 6.50 also shows how Weinreb amides of carboxylic acids can be obtained by C,C bond formation.

Fig. 6 21 Schematic views of G-protein coupled receptors, (a) Cross-sectional view of a G-protein coupled receptor demonstrating the N terminus in the extracellular space, seven transmembrane domains and the C terminus in the cytoplasm. (b) A view of the transmembrane domains of a G-protein coupled receptor from above demonstrating how amino acid side chains can form a precise ligand-binding site. In this example the ligand-binding site is shown to be formed by a side chain carboxylate group, two side chain amino groups and three side chain hydroxyls.

For other kinds of groups, where the electrometric titration curve must be used, we pick a region of pH within which only one of the of Eq. (10) is an unknown function of Z. In the acid region for example we may tentatively assume that the pKjnt of the usually small number of a-carboxyl groups is known. Side-chain carboxyl groups are the only other groups which are titrated in this range, so that Eq. (10) becomes... 

Tanford and Hauenstein showed that the acid part of the titration curve could be compatible with the same values of w as were used to fit the rest of the titration curve, if one were to assume that five of the ten side-chain carboxyl groups have pKint = 4.0, while five others have pKi t = 4.7. 

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