Amino Acids and Peptides: Zwitterions and the Peptide Bond · seed 1 · A4, ink-friendly. The answer key prints on its own page for grown-ups.

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Science · Chemistry · ages 21-22
Name ______________________   Date ____________

  1. Alanine has no ionisable side chain. At a pH far below both its pKa values, what is its main net charge?

    • Net charge -1
    • Net charge 0
    • Net charge +1

  2. Alanine has no ionisable side chain. Which main group states and net charge does it have near pH 7?

    • NH3+ and COOH; net charge +1
    • NH3+ and COO-; net charge 0
    • NH2 and COO-; net charge -1

  3. Most peptide bonds favour trans over cis geometry.

    Circle one:   True   False

  4. For free glutamic acid, use pKa 2.4 (alpha COOH), 4.4 (side-chain COOH) and 9.8 (NH3+). At pH 6, which dominant form, net charge and electrophoretic drift fit? Ignore fluid flow.

    • NH3+-CH(COO-)-CH2-CH2-COO-; net -1; drift toward the positive anode
    • NH3+-CH(COO-)-CH2-CH2-COOH; net 0; no net drift toward either electrode
    • NH2-CH(COO-)-CH2-CH2-COO-; net -2; drift toward the positive anode

  5. The two pKa values surrounding an amino acid's zero-charge form are 2.2 and 9.4. Use their average to estimate its isoelectric point.

    Answer: ______________

  6. Why are reactive groups outside the intended peptide-coupling pair protected when needed?

    • To activate the intended carboxyl group
    • To favour trans peptide geometry by increasing the amide rotation barrier
    • To mask unwanted coupling sites while leaving the chosen pair free

  7. A free carboxylic acid and amine often form a salt rather than a peptide. Why activate the carboxyl group for controlled peptide synthesis?

    • To make the carboxyl-derived group more reactive toward the amine
    • To mask reactive side chains during the intended coupling
    • To protonate the amine so its lone pair attacks the carbonyl faster

  8. An amino acid has successive pKa values 2.0, 4.0 and 9.5, with main charges +1, 0, -1 and -2 as pH rises. A student averages 2.0 and 9.5 to get pI = 5.75. Which correction follows the charge states?

    • Keep 5.75 by averaging the outermost pKa values
    • Use 2.0 and 4.0 around the zero-charge form, giving pI about 3.0
    • Use 4.0 and 9.5 around the negative-charge form, giving pI about 6.75
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Answer key

For grown-ups. Fold this page away before handing over the rest.

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  1. Net charge +1 · Both groups favour protonated forms. NH3+ contributes +1 and COOH contributes 0, giving net charge +1.
  2. NH3+ and COO-; net charge 0 · Near pH 7, alanine mainly has NH3+ and COO- groups. Their +1 and -1 charges sum to zero.
  3. True · Most peptide bonds favour trans because it reduces steric crowding. Cis bonds occur, with a larger cis fraction before proline.
  4. NH3+-CH(COO-)-CH2-CH2-COO-; net -1; drift toward the positive anode · pH 6 exceeds both carboxyl pKa values but is below the amino-group pKa. The dominant form has two COO- groups and one NH3+: net -1, with drift toward the positive anode.
  5. 5.8 · Average the supplied pair: (2.2 + 9.4) / 2 = 11.6 / 2 = 5.8.
  6. To mask unwanted coupling sites while leaving the chosen pair free · Protection masks groups that could react at unwanted sites while leaving the intended coupling groups available.
  7. To make the carboxyl-derived group more reactive toward the amine · Activation forms a carboxyl-derived species, such as an activated ester, that reacts more readily with the chosen amine.
  8. Use 2.0 and 4.0 around the zero-charge form, giving pI about 3.0 · The zero-charge form lies between the first and second proton losses. Average 2.0 and 4.0 to obtain pI about 3.0.
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