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MSc DRUG DISCOVERY AND DEVELOPMENT

MSc DRUG DISCOVERY AND PHARMA MANAGEMENT

MRES

PHAY0029

MODERN ASPECTS OF DRUG DISCOVERY

JANUARY 2020

SECTION A

DRUG DISCOVERY CASE STUDIES

1.        Answer BOTH parts of the question

(a)      Explain the relationship between the chemical structure of atenolol (shown below) and its clinical action as a beta blocker. (50 % of marks)

(b)      Using examples where relevant, explain the past, present and future importance of G-Protein Coupled Receptors as drug targets. (50 % of marks)

2.       Answer BOTH parts of the question

Developing small molecule inhibitors of protein-protein interactions has been regarded as a challenging area of drug discovery.

(a)      What factors make inhibiting the interactions between two proteins difficult? (30 % of marks)

(b)      What drug design strategies might be applied to develop protein-protein interaction inhibitors? Illustrate your answer with examples.     (70 % of marks)

SECTION B

TECHNIQUES IN DRUG DISCOVERY

3.       Answer ALL parts of the question

As part of a research project investigating the cytotoxic effects of a plant, you have treated HEPG2 cells with the plant material and collected cellular extracts for protein analysis. A one-dimensional sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis experiment revealed a protein band in the treated cellular extract that was not present in the untreated cellular extract, as demonstrated in the image below:

(a)      Explain how you could estimate the molecular weight of this protein band. (15 % of marks)

(b)      In order to identify the protein, you remove the band from the gel and carry out a trypsin digest of the protein prior to performing Matrix Associated Laser Ionisation - Time of Flight (MALDI-TOF) mass spectrometry analysis. Describe the MALDI-TOF technique and include in your answer a brief discussion of what the mass spectrum peaks would represent.             (50 % of marks)

(c)      After identification of the protein it becomes apparent that an antibody exists for this particular protein. Describe ONE method you could use for future screening of other cell extracts to detect the presence of the protein.        (35 % of marks)

4.         Answer ALL parts of the question

(a)        What causes peak broadening during the HPLC chromatographic separation process?         (60 % of marks)

(b)        How are peak broadening effects influenced by the mobile phase flow rate in isocratic and gradient modes of HPLC?    (15 % of marks)

(c)         In an experiment to separate two components by HPLC two peaks are seen on the chromatogram. Peak ”1” elutes with a retention time of 3.4 min while peak “2” elutes with a retention time of 3.8 min. The peak widths are 0.2 and 0.3 min for peak 1 and 2, respectively. Calculate the Resolution factor (Rs) value and decide if these two peaks are well separated based on the Rs value?                           (25 % of marks)

SECTION C

PHARMACEUTICAL INDUSTRY AND NEW TECHNOLOGY

5.       Answer ALL parts of the question

You are working for a life science consultancy company on a client project. The client company is a medium sized pharma company.

(a)      Describe the factors that determine business size.                   (10 % of marks)

(b)      The client company wishes to expand their global  market presence and are considering moving into an emerging market. Explain why emerging markets are attractive to pharma and, taking into account the strengths and weaknesses of a medium sized pharma company, give your opinion on whether they are likely to be successful.                        (60 % of marks)

(c)      The project you are working on involves an evaluation of pricing strategy for a new drug and therefore has a pharmacoeconomics section. Discuss the key aspects taken into account when using the Economic, Clinical and Humanistic outcomes (ECHO) model to analyse the outcomes for a new drug.          (30 % of marks)

6.       Answer ALL parts of the question

(a)      Compare the non-financial advantages and disadvantages of producing a protein biopharmaceutical from a cloned gene in bacteria, by chemical synthesis methods, or by extraction from a natural source.       (30 % of marks)

(b)      Discuss five specific difficulties of expressing a human gene in a bacterial host and explain the ways that these difficulties have been solved.   (40 % of marks)

(c)      Give a detailed explanation of how recombinant human growth hormone is produced in bacteria.         (30 % of marks)