1.For the amino acid glutamic acid,sketchon a single graphthe fraction protonated versus pH for all three ionizable groups. Your plot should contain three curves, onefor the carboxylategroup, one for the amino group, and one for the sidechain of Glu. You should assume the pKa values are 2.0 (main chain COOH), 4.0 (side chain) and 9.0 (main chain amino).
2.Proteins that regulate the expression of DNA in cells generally bind to the DNA by either hydrogen bonding, electrostatic (charge-charge) interactions, or both. These proteins contain a large number of lysine residues.
i) Explain how the presence of lysine residues would enhance the interaction (binding) of the protein to the DNA by both electrostatic and hydrogen bonding. Be sure to explicitly discuss how pH will affect the charge on the protein lysine residues and the DNA. Assume pH=7, the interaction is with the phosphate groups on DNA, and that the pKa of the lysine sidechain is 9 and the pKa of the phosphate group in DNA is 2.0. A partial structure of DNA is attached titled (DNA 2i).
ii) Mutations occur such that the some of the lysine residues on the protein are changed to glutamic acid. Predict how the DNA binding would change, would it get better, worse, or stay the same. Justify your answer
3.The structure of the drug thalidomide is attached titled (Drug 3)
i) Identify the chiral center on this molecule. Justify your answer .
ii) Because there are two forms of thalidomide (R and S), there may be different biological activities associate with each form. Briefly discuss what these may be .
iii) Why is it not possible to administer a pure enantiomer of thalidomide to avoid side-effects from the other enantiomer ?
4.A peptide (i.e. small protein) contains 10 amino acids. How many different peptides can exist that are 10 amino acids long? You can assume that an amino acid can be used more than once.
- For the tripeptide Ala-Thr-Gly:
i) Draw the chemical structure of a tripeptide. Your drawing should be appropriate for a pH=7.0.
Include all of the hydrogens, including those on carbon.
ii) Indicate all chiral centers on your diagram .
iii) Draw one water molecule donating a hydrogen bond to a main chain atom.
A picture of a small protein is attached titled (small protien), answer the following questions based on this picture:
i) Give the primary structure (amino acid sequence of the protein, N to C).
ii) Would you expect this short peptide to be highly soluble in water, partially soluble, or slightly soluble in water. Briefly justify your answer with reference to the amino acid side chains and the type of interaction the side chains would have with water.
Sample Solution