Name:
1
Chemistry 460 -- Exam #1 -- September 30, 2008
1. In a 2005 issue of The Journal of Organic Chemistry was an article entitled "StructureFunction Studies on a Synthetic Guanosine Receptor That Simultaneously Binds WatsonCrick and Hoogsteen Sites" (Quinn, J.R.; Zimmerman, S.C. JOC, 2005, 70, 7459). In this
article they described the design of a cytidine analog in which the amino group of the
cytidine was coupled to a carboxynaphthalene (see below) to make a new molecule 1 that
was able to bind more tightly to a guanosine analog than normal cytidine.
+
R-NH2
H2
Pd/C
EDC
NHR
CO2H
NO2
Carboxynaphthalene
Amino group
of cytidine
NHR
C
NO2
O
C
O
NH2
1
a) (10 pts) Draw the structure of the normal Watson-Crick pairing between cytosine and
guanosine. (Show the sugar attached to the guanosine, but just attach an R group to the
cytidine.)
b) (5 pts) Now draw the naphthalene analog attached to the amino group on the cytidine and
show how the presence of this group could lead to stronger binding with guanosine.
Name:
2
c) (5 pts) When placed in solution (a mixture of deuterated DMSO and CDCl3), the cytidine
analog binds to the guanosine analog with an association constant (Kassoc) of 2530 M-1 at
25 °C. What is ΔG° for this association? (R = 8.314 J/mol•K)
d) (5 pts) What would you estimate ΔG° to be for association of a similar cytidine analog that
lacks the NH2 group on the naphthalene ring? Explain. Is most of this change in ΔG° due to
a change in enthalpy or entropy?
e) (5 pts) Would you expect Kassoc to increase or decrease if the temperature is raised.
Explain your reasoning. (Hint: Think about how ΔG will change as the temperature is
raised.)
Name:
3
2. In 1997 Yarger, Nieman, and Bieber published a paper in the Journal of Chemical
Education entitled "NMR Titration Used To Observe Specific Proton Dissocation in
Polyprotic Tripeptides" (Yarger, J.L.; Nieman, R.A.; Bieber, A.L. J. Chem. Educ. 1997, 74,
243-246). Their data for the titration of the tripeptide Gly-Tyr-Gly are shown below. You
can see that when a particular group changes protonation state, the chemical shift of nearby
protons shift. The chemical shift that is observed is the weighted average of the shift in the
protonated and deprotonated forms. By analyzing the chemical shift as a function of pH the
pKa of various groups in peptides (and even proteins) can be determined.
a) (10 pts) Draw the structure of GlyTyrGly at pH 1.5, 6.9, and 11.8.
Name:
4
b) (5 pts) In the pH 11.8 spectrum the protons on the α-carbon of one glycine appear between
3.6 and 3.9 ppm, while the protons on the α-carbon of the other glycine appear between 3.2
and 3.4 ppm. By inspection of their pH dependent behavior determine which protons
correspond to the amino terminal glycine and which ones belong to the carboxyl terminal
glycine. Clearly explain your reasoning.
c) (5 pts) For the tyrosine aromatic proton that shows the largest change in chemical shift
between the protonated and deprotonated forms, determine (by inspection of Figure 3) the
chemical shift in the fully protonated and deprotonated states. Also provide your estimate
for the pKa of the tyrosine side chain.
d) (10 pts) Using your values in part c, and remembering that the observed chemical shift is
the weighted average of the shifts in the protonated and deprotonated states, derive an
expression that gives the chemical shift as a function of pH. (This is similar to what you did
when you used excel to plot the theoretical absorbance of 4-nitrophenol as a function of pH.)
Name:
5
e) (10 pts) Yarger, Nieman, and Bieber also studied the tripeptide Glu-Tyr-Glu. Draw the
structure of this peptide (clearly showing the correct (L) stereochemistry at the α-carbons) at
pH 7. Would you expect the pKa for the tyrosine side chain to be higher or lower than that
found for Gly-Tyr-Gly? Briefly explain.
f) (10 pts) In their paper, Yarger, Nieman, and Bieber state that "Sodium hydrogen phosphate
(NaxH3-xPO4) was used to make up 50 mM buffer solutions in the pH range of 2-13."
Describe how to prepare 5 mL of this buffer at pH 7.8. Assume you have 0.50 M stock
solutions of each of the sodium hydrogen phosphates. (Don't use a pH meter in your
procedure.)
Acid
pKa
H3PO4
2.15
H2PO4-
6.82
HPO42-
12.38
Name:
6
3) (10 pts) In an article in the Journal of Dental Research (Dabelsteen, E.; Goo, S. J. Dent.
Res. 2005, 84, 21-28) titled "ABO Blood-group Antigens in Oral Cancer" they drew the
following shorthand notation to depict the antigen precursor Ley which is upregulated in
migrating breast carcinoma cell lines. Draw the full structure for this carbohydrate. (Recall
that Fuc is short for L-Fucose. Fucose is 6-deoxygalactose.)
Gal!1-4GlcNAc!1-R
2
3
Fuc"1 Fuc"1
4) (10 pts) Cells are surrounded by "lipid bilayers".
a) Draw a generic structure for the major class of molecules that make up a lipid bilayer.
(Provide general details about the structure of the various parts of these molecules.)
b) Draw a picture to depict how these molecules are organized in a lipid bilayer. (This may
be a schematic picture, you don't have to show every atom, but be sure to identify the various
parts of the molecules and where they appear in the structure.)
c) An article in the Biophysical Journal (Abreu, M.S.C., Moreno, M.G.; and Vaz, W.L.C,
Biophysical Journal, 2004, 87, 353-365) looked at the thermodynamics of association of
different lipids into a lipid bilayer and found that the process was sometimes endothermic
and sometimes exothermic depending on the structure of the lipid, however the sign of the
entropy term for this process was always the same. Is the entropy change associated with
these lipids moving from aqueous solution into a bilayer greater than zero or less than zero?
Explain why it is greater or less than zero.