ACJC_H2_CHEM_P3_Answers Prelim

2 © ACJC 2015 9647/03/Prelim/15 [Turn over Answer any four questions. 1 (a) Bradykinin is a nonapeptide ( polypeptide with nine residues) which is a pain - causing agent. Complete hydrolysis of this polypeptide yields the following amino acids. Amino acid Pro Ser Arg Gly Phe No. of residues 3 1 2 1 2 Partial acid hydrolysis of bradykinin gave the following di- and tripeptides. Phe-Ser; Pro-Gly-Phe; Pro-Pro; Ser-Pro-Phe; Phe-Arg; Arg-Pro Given that both the terminal residues in the nonapeptide are arginine (Arg), deduce the primary structure of bradykinin. Arg-Pro Pro-Pro Pro-Gly-Phe Phe-Ser Ser-Pro-Phe Phe-Arg Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg [2] (b) Frederick Sanger used 2,4-dinitrofluorobenzene (2,4-DNFB) in a basic solution to bind to the free amino group of the N -terminal of a polypeptide thereby labelling the N-terminal residue leading to its identification after hydrolysis. The reaction is shown below:

3 © ACJC 2015 9647/03/Prelim/15 [Turn over A nucleophilic aromatic substitution occurs between 2,4-DNFB and the N-terminal residue in the first step of the process. (i) Suggest why a basic solution is used in reaction step 1, involving 2,4-DNFB and the peptide. N-terminal is usually protonated at physiological/normal pH. Hence need to use a base to deprotonate the amino group so that it can act as a nucleophile. [1] (b) (ii) Generally, halobenzenes do not undergo nucleophilic aromatic substitution. However, in the above reaction, 2,4 -DNFB seemingly undergoes nucleophilic aro matic substitution. Explain why this is possible , in this instance. Fluorine is very electronegative and hence produces a partial positive charge on the carbon atom to which is bonded, drawing the nucleophile. The two strongly electron withdrawing nitro groups help to disperse the negative charge in the reactive intermediate thereby stabilising it. [2] (c) Emil Fischer used the following reaction scheme to convert serine into alanine.

4 © ACJC 2015 9647/03/Prelim/15 [Turn over (i) Draw the structural formula for A and state the type (s) of reactions that have taken place. Acid-base reaction (no “neutralisation”) and esterification/condensation/nucleophilic (acyl) substitution [3] (ii) Draw the structure of B and use it to explain why the first step is necessary for the overall conversion of serine into alanine. Esterification of the carboxyl group is necessary to prevent it from being converted to the acyl chloride which will render