Question

Given below are two statements, one is labelled as Assertion (A) and other one labelled as Reason (R).
Assertion (A) : Depsipeptides have more flexible structure and lower rotational barrier for cis-trans isomerization than their native analogs.
Reason (R) : One or more amide linkages in depsipeptides are replaced with corresponding ester groups leading to their reduced hydrogen bonding capacity, which in turn results in deformed secondary structures.
In light of the above statements, choose the correct answer from the options given below.

• A. Both (A) and (R) are true and (R) is the correct explanation of (A).
• B. Both (A) and (R) are true but (R) is NOT the correct explanation of (A).
• C. (A) is true but (R) is false.
• D. (A) is false but (R) is true.

Hint:

Depsipeptides are commonly found in nature as cyclic natural products (such as the antibiotic Valinomycin) and are investigated in protein engineering to probe the role of backbone hydrogen bonds in protein folding.

Answer 1

The Correct Option is A

Step 1: Understanding the Concept:
Depsipeptides are structural analogs of peptides where one or more amide bonds ($-\text{CONH}-$) are replaced by ester bonds ($-\text{COO}-$).
This chemical modification significantly alters the physical properties, backbone conformational dynamics, and secondary structures of the polymer.

Step 2: Detailed Explanation:
Let us analyze both the Assertion and the Reason:
- Assertion (A): Depsipeptides possess more flexible backbone structures and display significantly lower rotational energy barriers for cis-trans isomerization of the peptide backbone compared to their native amide-linked analogs.
The ester linkage introduced into the backbone has different stereoelectronic properties compared to the amide linkage, which increases conformational freedom.
Thus, Assertion (A) is true.
- Reason (R): The replacement of one or more amide linkages with ester groups alters the hydrogen bonding profile of the peptide.
An amide bond contains both a hydrogen bond donor ($-\text{NH}-$) and an acceptor ($-\text{C}=\text{O}$).
An ester bond lacks the amide hydrogen atom ($-\text{NH}-$), removing a key hydrogen bond donor.
This loss of hydrogen-bonding donors reduces the overall stability and density of the intramolecular hydrogen-bonding network that stabilizes alpha-helices and beta-sheets.
The reduction in hydrogen-bonding capacity deforms the canonical secondary structures and increases backbone flexibility, which lowers the energy barrier for cis-trans isomerization.
Therefore, Reason (R) is true and provides the correct chemical explanation for Assertion (A).

Step 3: Final Answer:
Both (A) and (R) are true, and (R) is the correct explanation of (A), corresponding to option (A).