O S O. Sodium dodecyl sulfate

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1 ame: TF ame: LS1a Fall 06 roblem Set #2 100 points total All questions should be turned in. 1. (26 points) Sodium dodecyl sulfate, or SDS (also known as sodium lauryl sulfate) is a common detergent found in many commercial soaps. It is an amphipathic molecule which means it has both hydrophobic and hydrophilic regions. hydrophobic end a S hydrophilic end Sodium dodecyl sulfate (a) Briefly explain how SDS helps to solubilize oily substances (such as the triacylglycerides you saw in problem set #1) in liquid water. (6 points) Detergents such as SDS can bind to the hydrophobic portion of the triacylglyceride with its hydrophobic end, leaving the hydrophilic end of the detergent to interact with water. This way the hydrophobic portion of triacylglyceride is coated with hydrophilic groups so the oily substance is now more soluble in an aqueous solution. Similarly, the body makes use of bile acids to solubilize fatty substances that pass through the digestive system. This allows the body to absorb hydrophobic nutrients via the small intestine. Shown below is the bile acid cholic acid; note the general hydrophobic character of the cyclic portion of the molecule: Cholic acid pka = ~5 (b) Given the pka of the acid, what is the ratio of the deprotonated form to the protonated form at each given p? deprotonated : protonated At p 5? 1 : 1 (2 points) At p 6? 10 : 1 (2 points) At p 7? 100 : 1 (2 points)

2 ame: TF ame: To improve upon the detergent properties of cholic acid, the body attaches it to taurine (a common additive found in many energy drinks). Taurine Taurocholic acid 2 S S pka = ~2 (c) Given the pka of the the sulfonate group (the group pointed to by the arrow), what is the ratio of the deprotonated form to the protonated form at each given p? deprotonated : protonated At p 5? 1000 : 1 (2 points) At p 6? 10,000: 1 (2 points) At p 7? 100,000: 1 (2 points) (d) If the average p of the duodenum (the first segment of the small intestine) is ~ 6, why might taurocholic acid be better at solubilizing fats in the duodenum than cholic acid? (8 points) Taurocholic acid is better at solubilizing fats in the duodenum since it acts as a better detergent than cholic acid at p 6. The deprotonated form of the bile acid is more hydrophilic, interacts more strongly with water, and therefore is better at solubilizing the fats. Taurocholic acid has a ratio of 10,000:1 deprotonated to protonated whereas cholic acid has a rate of a mere 10:1 deprotonated to protonated. Thus, taurocholic acid is a more effective detergent at p 6.

3 ame: TF ame: 2. (26 points) Shown below on the left is part of a protein interacting with part of a DA strand (it should look familiar as you saw it in problem set #1). Consider what would happen to the DA/protein interaction at various p's. Two relevant pka values are shown to the right. protein 2 2 DA DA R 2 pka 12.5 R pka 2 R (a) Draw the protein/da interaction at p= 7 (make sure to include formal charges!) protein DA DA (6 points) The protein is positively charged and the phosphate is negatively charged. They will interact ionically. They can also form hydrogen bonds (shown by dotted lines), however hydrogen bonds are much weaker than an ionic bond. (b) Draw the protein/da interaction at p= 1. protein DA DA (6 points) The phosphate will be protonated, and have no net charge. The protein and DA will not ionically interact with one another. owever, hydrogen bonding can still occur.

4 ame: TF ame: (c) Draw the protein/da interaction at p= 13. protein DA DA (6 points) The arginine residue will be deprotonated and have no net charge. The protein will not ionically interact with the negatively charged phosphate. owever, hydrogen bonding can still occur. (d) At which p value(s) would the interaction be the strongest? the weakest? Explain your answer in three sentences or less. (8 points) nly at p 7 does an ionic interaction exist between the two molecules, and thus this is where the interaction is strongest. At the other two p s, one molecule is charged while the other is uncharged. They should have equivalent strengths of interaction due to the hydrogen bonds that occur weaker than the ionic interaction.

5 ame: TF ame: 3. (20 points) Shown below are the standard DA base pairs, AT and GC: C 3 Adenine Thymine Guanine Cytosine A biotech company has recently synthesized a pyrimidine-substitute (we ll call it A ), shown below: "A" (a) Which purine (A or G) would form a stronger base pair with A when in a standard double helix of DA? Draw in your matched and mismatched pairs below (the basic, incomplete purine skeleton has been provided for you simply fill in the missing groups present on A or G), and rationalize your choice. MATCED: MISMATCED: Guanine "A" Adenine "A" (10 points) Guanine would form a stronger base pair with A. It can form multiple hydrogen bonds with A (the three parallel hydrogen bonds should be drawn in for full credit, a couple others are also possible) whereas adenine cannot. [ote: There might be also be steric repulsion between A and A if the 2 group of A overlaps in space with some of the groups in A.]

6 ame: TF ame: The biotech company also offers a chemical Cap that can be appended to the 5 end of a DA strand: DA "Cap" (b) Do you think this Cap when present at the 5 end of a DA strand would promote or disrupt DA duplex formation? Why? Describe a key molecular interaction in your answer. (10 points) This 5 cap would promote DA duplex formation. It would promote the stacking interactions between bases (hydrophobic effect). It would also strengthen the hydrogen bonds at the end of the strand by shielding them from attack by solvent.

7 ame: TF ame: 4. (10 points) In 2001, eter ielsen developed a peptide analog of DA, called a peptide nucleic acid (A). The basic structure of the A is shown below (the structure of DA is also shown, for comparative purposes: Base Base Base Base A DA Despite the differences in the backbone, it was found that A strands form stronger base-paired duplexes than their corresponding DA duplexes. (a) Why might a A duplex be stronger than a DA duplex? Explain (IT: A duplexes are stable in pure water, whereas DA duplexes are unstable in pure water) (10 points) The backbone of A is polar, but not negatively charged like the phosphate-ribose backbone of DA. Therefore, the A backbone chains do not repel one another like the DA backbone chains do. In regular water, cations help ameliorate the close proximity of two negatively charged strands of DA, but in hyper-pure water no cations are present to neutralize the negative charges.

8 ame: TF ame: 5. (18 points) Dimethyl phosphoric acid is structurally similar to the phosphates in the backbone of DA. Shown below is the deprotonation of dimethyl phosphoric acid: 3 C 3 C 3 C C Abbreviated as: A B + + (a) Write out equation for the acidity constant (K a ) of dimethyl phosphoric acid (use the abbreviations A and B for your equation) (2 points) K a = [B] [ + ] [A] (b) Experimentally, the K a is determined to be What is the approximate pka value? (2 points) pk a = -log K a = -log (0.05)=1.3 (c) What is the relative ratio of A and B at p 7.0? (6 points) pk a = p + log [A]/[B] 1.3 = log [A]/[B] 5.7 = - log [A]/[B] = [A]/[B] During the race to solve the structure of DA, Linus auling proposed a triple-helical structure based on the following structure (as viewed from the top of the helix): (d) In light of what you know, why is this structure is not plausible in a cellular context?

9 ame: TF ame: (8 points) The pka of dimethyl phosphoric acid is similar to that of the phosphates in the backbone of DA. At cellular p 7.0, the phosphates in the DA backbone will not be appreciably protonated (see answer to c). There will be roughly one neutral protonated phosphate for every one million deprotonated negatively charged phosphates at p 7. Thus, auling s structure is implausible as it is dependent upon the phosphates being protonated inside the cell and hydrogen bonding with one another; the vast majority of phosphates in a cellular context will be negatively charged and would repel one another, so this triple helix could not exist.