Amino acids residues of a peptide

The amino group of the N-terminal amino acid residue of a peptide will react with the FDNB reagent to form the characteristic yellow DNP derivative, which may be released from the peptide by either acid or enzymic hydrolysis of the peptide bond and subsequently identified. This is of historic interest because Dr F. Sanger first used this reaction in his work on the determination of the primary structure of the polypeptide hormone insulin and the reagent is often referred to as Sanger s reagent. 

The value Q given represents the average hydrophobicity of a peptide and is obtained by summing the f-values of the amino acid residues of a peptide and dividing by the number of the amino acid residues. 

Almost all peptides of hydrophobic L-amino acids elicit a bitter taste, which indicates that the bitterness of peptides is caused by the hydrophobic property of the amino acid side chain. Ney (12) has reported that whether a peptide has a bitter taste or not depends on its hydrophobic value Q. The value Q is obtained by adding the Af-values (Table 3) of each constituent amino acid residue of a peptide and dividing the sum by the number of amino acid residues (n). 

C-terminal end group analysis, determination of the C-terminal amino acid residue of a peptide or protein. The analysis can be performed chemically by the Aka-bori method, or enzymatically by the car-boxypeptidase (CP) approach. CP with different specificities are capable of liberating C-terminal amino acids. 

Dinitrofluorobenzene will react with any free amino group in a polypeptide, including the e-amino group of lysine, and this fact complicates Sanger analyses. Only the N-terminal amino acid residue of a peptide will bear the 2,4-dinitrophenyl group at its a-amino group, however. Nevertheless, the Edman method of N-terminal analysis is much more widely used. ... 

Sat er A-terminal analysis (Section 24.5B) A method for determining the A -terminal amino acid residue of a peptide by its SiqAr (nucleophilic aromatic substitution) reaction with dinitro-fluorobenzene, followed by peptide hydrolysis and comparison of the product with known standards. 

Fewer methods are available to identify the C-terminal amino acid residue of a peptide. When the peptide is heated to 100°C (for about 12 hours) with hydrazine (NH2NH2), the amide bond of each residue is attacked and cleaved. The products are amino hydrazides. If tripeptide ala-val-leu (190) is heated with hydrazine, there are two amide bonds and the products are alanine hydrazide (191), valine hydrazide (192), and leucine (55). The C-terminal amino acid is not converted to the hydrazide because hydrazine reacts with the amide rather than with the free carboxyl group. 

Amino acid residues (Section 27.7) Individual amino acid components of a peptide or protein. 

Alzheimer s Disease. Figure 2 A(3 is derived from the APP by the sequential action of proteolytic activities exerted by (3- and y-secretases. APP-CTF is (C99) produced after cleavage of the APP by (3-secretase and represents the substrate of the y-secretase. The yellow box marks membrane embedded amino acid residues of A(3 peptide. Scissors represent the main cleavage sites of (3- and y-secretase, e.g. the e- and y-cleavages at positions 49,46, 42, 40 and 38. 

Figure 4-6. The Edman reaction. Phenylisothiocyanate derivatizes the amino-terminal residue of a peptide as a phenylthiohydantoic acid. Treatment with acid in a nonhydroxylic solvent releases a phenyithiohydantoin, which is subsequently identified by its chromatographic mobility, and a peptide one residue shorter. The process is then repeated.

Proteins are fundamentally polymers of a-amino acids linked by amide linkages (see Section 13.1). It is a pity that biochemists refer to these amide linkages as peptide bonds remember, a peptide is a small protein (less than about 40 amino acid residues), whereas a peptide bond is an amide. Therefore, peptides and proteins may be hydrolysed to their constituent amino acids by either acid or base hydrolysis. The amide bond is quite resistant to hydrolytic conditions (see above), an important feature for natural proteins. 

Figure 9.36 shows Newman projections of the three low-energy conformers for the Ca-Cp bond of an AMX amino acid residue within a peptide or protein. The gauche relationship should give a small coupling (<6 Hz) and the anti relationship should give a... 

Fig. 8-4 The mechanism of covalent catalysis of the hydrolysis of a C-terminal amino acid residue from a peptide by carboxypeptidase A. The reaction is (a) —> (d), and the bold line structure is the peptide substrate. The C-terminal tyrosine side chain of the substrate shown in (a) is denoted by in (ft), (c), and (d).

Racemization is thought to proceed by abstraction of the ct-proton from an amino acid or amino acid residue in a peptide or protein to give a negatively charged planar carbanion (11 Figure 1). A proton can then be added back to either side of this optically inactive intermediate, thus regenerating the L-form or producing the D-enanticmer. The reaction can be written as... 

Figure 4.20. Determination of the Amino-Terminal Residue of a Peptide. Dabsyl chloride labels the peptide, which is then hydrolyzed with the use of hydrochloric acid. The dabsyl-amino acid (dabsy 1-alanine in this example) is identified by its chromatographic characteristics.

There are direct consequences of the amino-acid make-up and sequence of amino-acid residues within a peptide (its primary structure) on its overall conformational behaviour. In spite of the regularity of the backbone of the molecule, a wide variety of conformations is adopted, indicating the role of the side-chains in determining the overall conformation of the molecule. 

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