FINAL EXAM - CHEM 168 Total points: 80 26. (4+2 points) A pharmaceutical company
ID: 214635 • Letter: F
Question
FINAL EXAM - CHEM 168 Total points: 80 26. (4+2 points) A pharmaceutical company is interested in developing peptides for targeting protein biomarkers. The company has recently become very interested in developing peptides (30 amino acids) that target heat shock protein 90 (Hsp90). a) Suggest a practical scheme by which a peptide could be directly evolved from a random library of peptides. What technique would you use, and how would the selection step be performed (be sure to specify what probes/protocols you would need to use for the selection). b) Using your aforementioned strategy, the company discovers an alpha helical peptide that binds to Hsp90 with aExplanation / Answer
26(a) ANSWER
There are several methods by which a peptide could be directly evolved from a random library of peptides such as receptors, target molecules, enzymes, monoclonal and polyclonal antibodies. Random library of peptides are a collection of peptides i.e. sequences of different ranges from 1 million to 1 billion. These library helps pharmaceutical company by providing ligands that work as leads.
Among above mentioned method, DNA display system facilitates many advantages over other methods. Anti FLAG M2 antibody-agarose beads are used to elute FLAG peptide. This is the affinity selection of peptides. Then amplification and translation of DNA occurs which is analyzed by Dot blot method using M2 antibody. Peptides bind with M2 antibody. Then Protein Microarray technique is used to track the peptide. It is a secondary screening of peptide as earlier affinity method used for same work.
Advantages
1. Chemical stability of DNA
2. Facilitate off rate selection of high affinity binders over a longer period.
3. Able to evolved proteins that work under severe conditions.
4. Useful to study protein-protein and drug-protein interaction.
26b) ANSWER
Cell penetrating peptides (CPPs) are capable to deliver a peptide within a cell by crossing plasma membrane. These systems are versatile and efficient to deliver peptides inside the cell. To prevent degradation of peptides from proteases Pegylation is one of the best method among others. It is a process in which polyethylene glycol chains attach to peptides and prevent the degradation of peptides by proteases.
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