Assignment 1 for Weeks 1-4 (15% of total) NAME: __________________________ ID: _______________________________ Question 1 (5 points) 1. The hydrolysis of oligonucleotides obtained from DNA is slow under most conditions. In contrast, 100mM NaOH (aqueous, pH 12.88) results in rapid hydrolysis of oligonucleotides from RNA. Suggest why this is the case by providing a plausible mechanism. Also, suggest a way how you would modify the RNA nucleotide to slow down the hydrolysis. Question 2 (10 points) 2. Discuss all the non-covalent interactions involved in stabilizing the double helical structure of DNA in water at physiological pH. Question 3 (10 points) 3. Draw a diagram of both an A:T and G:C Watson Crick base pair. By considering the functionalities exposed in major and minor groove, comment on which groove provides the best discrimination for molecular recognition between an A:T versus T:A base pair? What about an G:C versus C:G base pair? Explain your rationale. Question 4 (5 points) 4. The oligopeptide-based drug Netropsin (shown below) is an active antiviral agent that targets double stranded DNA. a. Describe which part of the DNA structure is targeted by Netropsin and what binding interactions facilitate the formation of the DNA-Netropsin complex. (3 points) b. What physiological process might Netropsin inhibit by forming such a complex with DNA? (2 points)