Exam2. You are a scientist at a pharmaceutical company and want to develop a new

Question

Exam2. You are a scientist at a pharmaceutical company and want to develop a new drug that can decrease heart rate. In order to do this you decided to target the beta 2 adrenergic receptor. You want to design a peptide that gets incorporated into the plasma membrane and interferes with beta 2 adrenergic receptor signaling. 1) Design the peptide sequence (10) and describe briefly each of the features and function of the sequences you incorporated (20). (1sentence for each) 2) How would you test that the peptide is delivered to the plasma membrane ( 3 approaches), and that it is interfering with beta 2 adrenergic receptor signaling (3 approaches) (20). What are the advantages and disadvantages (3 each) of your approaches used (5). Maximum 10 sentences each. 3) How would you determine if the exocytosis (7) and endocytosis (7) of the beta 2 receptor is still occurring. What are the drawbacks of your approach (6). (10 sentences maximum for each) 4) How would you test if your peptide is folded correctly in the cells without having to determine its structure. (Hint, what signaling pathways get activated by unfolded proteins (3 approaches) (10). How would you block these pathwaysthat are activated specifically for your peptide (3 approaches) (10). What are the disadvantages and advantages of your method (3 each) (5). Maximum 10 sentences each.

Explanation / Answer

1) See, the beta2 adrenergic receptor (short form ADRB2) is present in the cell membrane. It interacts with epinephrine/adrenaline to produce the signaling response.

In this question, you have to prepare a protein that interacts with the ADRB2. So, the peptide sequence should resemble C - terminal of the receptor. After binding with the receptor, it will disallow binding of adrenaline and the ADRB2. So, adenylyl cyclase will not be produced, and cAMP will not be generated. Further, phosphorylation of PKA will not occur and finally, Ca channels will not be opened.

The protein is: -

C-HQGTVPSDNIDSQ

2) ELISA technique can be used to test whether the peptide has bound to ADBR2 or not.

Advantages: - Easy to use and user friendly.

Disadvantage: - ADBR2 gene does not have introns. So, different polymorphic forms of this gene are known. These polymorphic forms may be related with obesity, point mutations, nocturnal asthma etc. So, you actually don't know that the peptide has actually bound to the required ADBR2 gene (affecting heart rate); or it has bound to some other polymorphic form of the gene.

***Hope it helps. Please post other parts separately for detailed answers.

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