Biolink 'Drugs and their Conformations' (a) Which drug is more likely to produce multiple physiological effects: a drug with conformational flexibility or a drug with a rigid structure? Explain. (b) Using the example of HIV drugs, describe how conformation flexbility helps us keep up with drug resistance.
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- Prepare a schematic diagram and present it. The Figure should illustrate the interactions made between the key components of total and non-specific binding reactions in drug bindings. In preparing this figure, it should reflect on the role of each of the components of the reaction mixtures, and why the subtraction of non-specific from total binding allows us to calculate specific binding. The Figure Legend should be brief but informative.2.Pharmacodynamics: Drug Receptors subserve two essential functions: (1) recognition of the specific ligand molecule (2) transduction of the signal into a response. Accordingly, the receptor molecule has a ligand binding domain (spatially and energetically suitable for binding the specific ligand) and an effector domain which undergoes a functional conformational change. These domains have now actually been identified in some receptors. The perturbation in the receptor molecule is variously translated into the response. Considerable progress has been made in the understanding of transducer mechanisms which in most instances have been found to be highly complex multistep processes that provide for amplification and integration of concurrently received extra- and intracellular signals at each step. Because only a handful of transducer pathways are shared by a large number of receptors, the cell is able to generate an integrated response reflecting the sum total of diverse signal input.…(1) Discuss the structure and function of ion channels and describe their importance in medicinal chemistry. (ii) Draw the molecular structure of tamoxifen and discuss, in detail, its mode of therapeutic activity. Use the protein databank (PDB entry: 3ERT) to help support your answer.
- . Describe how studying 3-D structures of PTGS1 and PTGS2 could help researchers design a drug that binds to PTGS1, but not to PTGS2.Experiment This experiment was designed to analyze the structure of a component (C3c protein) of the complement system, which is involved in the immune response against microorganisms. Purified C3c protein (molecular mass: 145 kd) was incubated in the presence of various concentrations of the reducing agent dithiothreitol (DTT) and then subjected to electrophoresis in a sodium dodecyl sulfate (SDS)-polyacrylamide gel. SDS disrupts noncovalent bonds and polypeptides are separated by size during electrophoresis. The gel was stained with Coomassie Brilliant Blue, a protein dye. The figure shows the molecular masses of intermediates and products generated by DTT treatment. Results: Molecular mass (kd) 145- 102- 75- 43- 27- [DTT] (MM) 10.00 1 2 3 4 5 6 Samples Questions 1. How many polypeptides are present in C3c? Determine their molecular masses from the figure. What was the purpose of using DTT in this experiment? What kind of bonds hold the polypeptides 2. 3. together? 4. How is the 102…Experiment This experiment was designed to analyze the structure of a component (C3c protein) of the complement system, which is involved in the immune response against microorganisms. Purified C3c protein (molecular mass: 145 kd) was incubated in the presence of various concentrations of the reducing agent dithiothreitol (DTT) and then subjected to electrophoresis in a sodium dodecyl sulfate (SDS)-polyacrylamide gel. SDS disrupts noncovalent bonds and polypeptides are separated by size during electrophoresis. The gel was stained with Coomassie Brilliant Blue, a protein dye. The figure shows the molecular masses of intermediates and products generated by DTT treatment. Results: Molecular mass (kd) 145- 102- 75- 43- 27- [DTT] (MM) 1 2 3 4 5 6 Samples Questions 3. What kind of bonds hold the polypeptides together? |
- Signal Transduction 10. When a primary signal needs to be sent to most cells throughout a multicellular organism, the signal most suited for this is a A) neurotransmitter. B) hormone. C) dissolved gas. D) transcription factor. E) translation elongation factor Answer: Explanation:Experiment This experiment was designed to analyze the structure of a component (C3c protein) of the complement system, which is involved in the immune response against microorganisms. Purified C3c protein (molecular mass: 145 kd) was incubated in the presence of various concentrations of the reducing agent dithiothreitol (DTT) and then subjected to electrophoresis in a sodium dodecyl sulfate (SDS)-polyacrylamide gel. SDS disrupts noncovalent bonds and polypeptides are separated by size during electrophoresis. The gel was stained with Coomassie Brilliant Blue, a protein dye. The figure shows the molecular masses of intermediates and products generated by DTT treatment. Results: Molecular mass (kd) 145- 102- 75- 43- 27- [DTT] (MM) 10.00 1 2 3 4 5 6 Samples Questions 4. How is the 102 kd polypeptide related to the other polypeptide species?Select all that apply: The aim of the fentanyl project in Baker's group is to do the following to detect the biohazard: | a. Grow the genetically engineered organisms in areas where the biohazard may be deployed. | b. Generate a customized protein that is modified to glow when fentanyl binds to the receptor site. | c. Genetically engineer thale cress to produce customized proteins that they have designed. | d. Custom engineer proteins that glow with fentanyl for use in a spray that can be applied in the field. O e. Modify one of the proteins found in thale cress to glow when fentanyl binds to the receptor site.
- Other than the substitution of uracil for thymine, how doRNA nucleotides differ from DNA nucleotides? (Hint: Reviewsection 2.4.)From a medicinal chemistry (and a pharmacologist) perspective, functional groups provide specific properties and behaviors that allow drug molecules to exert their desired PD and PK effects. The key point here is that each individual group within a drug molecule can serve to provide one or more specific roles, tasks, or functions. The following table summarizes a series of drug discovery lead optimization for targeting a certain renal disease. Explain the basis for changing the R- functionality at the para- position. Please explain in as much detail as you need and by using scientific justifications, which one of the 4 candidates (526-529), presents the most viable investigational drug candidate, given the information provided below? N- `N' 'N' R- Drug Code R IC30 (nM) Half-Life (tı2), Minutes 526 CH;O 104 6 527 CF;0 1110 95 528 CH;CH, 11 <5 529 CH,CF, 14 96. It has been postulated that the normal (noninfectious) form of prion differs from the infectious form only in secondary/tertiary structure. (a) How might you show that changes in secondary structure occur? (b) If this model is correct, what are the implications for structural prediction schemes?