Q.35 Polypeptides are biosynthesized on the ribosomes inside the cell. Chemical synthesis of
polypeptides is also possible through Merrifield’s solid-phase peptide synthesis. In both the cases the
polypeptide chain is extended one amino acid at a time. The direction of polypeptide synthesis is from
(A) C-terminus to N-terminus in both the cases
(B) N-terminus to C-terminus in both the cases
(C) C-terminus to N -terminus on the ribosomes and N -terminus to C -terminus in solid-phase synthesis
(D) N-terminus to C-terminus on the ribosomes and C-terminus to N-terminus in solid-phase synthesis
The correct answer is (D) N-terminus to C-terminus on the ribosomes and C-terminus to N-terminus in solid-phase synthesis.
Introduction to polypeptide synthesis
Polypeptides are linear chains of amino acids that have an N-terminus (free amino group) and a C-terminus (free carboxyl group), giving every protein a defined directionality. Inside cells, ribosomes synthesize polypeptides during translation, while in the lab, chemists often use Merrifield’s solid-phase peptide synthesis to build peptides step by step.
Direction of synthesis on ribosomes
During biological protein synthesis, ribosomes read mRNA from 5′ to 3′ and add each new amino acid to the C-terminal end of the growing polypeptide. As a result, the polypeptide chain is synthesized from the N-terminus to the C-terminus; the first amino acid retains a free amino group, and the last amino acid contributes the terminal carboxyl group.
Key points:
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The first amino acid (often methionine) provides the free N-terminus of the protein.
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Every incoming amino acid’s carboxyl group forms a peptide bond with the free amino group at the C-terminal end of the growing chain, extending the chain toward the C-terminus.
Direction of Merrifield solid-phase peptide synthesis
In Merrifield’s solid-phase peptide synthesis, the peptide is grown while anchored to an insoluble resin through its C-terminus. Chemists sequentially add protected amino acids so that each new residue is attached via its carboxyl group to the free amino group of the immobilized peptide, effectively assembling the peptide from C-terminus to N-terminus.
Key points:
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The first amino acid’s C-terminus is covalently linked to the solid support, thereby defining that end as the future C-terminus of the peptide.
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Successive amino acids are added to the free N-terminus of the growing peptide, so chemical synthesis proceeds in the opposite direction to ribosomal synthesis (C→N in terms of chain extension).
Explanation of all options
Option (A) C-terminus to N-terminus in both the cases
This option is incorrect because it contradicts the well-established direction of translation on ribosomes, which is N-terminus to C-terminus. Ribosomes never synthesize polypeptides from C-terminus to N-terminus; the last amino acid added always becomes the new C-terminus.
Option (B) N-terminus to C-terminus in both the cases
This option is partially correct but overall incorrect. While ribosomal synthesis indeed goes from N-terminus to C-terminus, Merrifield’s solid-phase peptide synthesis grows the peptide from C-terminus to N-terminus because the first residue is attached to the resin through its C-terminal group.
Option (C) C-terminus to N-terminus on the ribosomes and N-terminus to C-terminus in solid-phase synthesis
This option reverses the actual situation and is therefore incorrect. In reality, ribosomes elongate polypeptides from N-terminus to C-terminus, whereas solid-phase chemical synthesis extends the chain in the opposite direction, from C-terminus to N-terminus.
Option (D) N-terminus to C-terminus on the ribosomes and C-terminus to N-terminus in solid-phase synthesis
This option correctly states that biological protein synthesis on ribosomes proceeds from N-terminus to C-terminus, while Merrifield solid-phase peptide synthesis extends the peptide from C-terminus to N-terminus. Hence, option (D) is the correct answer for this question on the direction of polypeptide chain extension in biological vs chemical peptide synthesis.
