Nascent polypeptide chain (NPC)

The nascent polypeptide chain is an amino acid sequence as it is being synthesized by the ribosome, preceding its release and full folding into a functional protein. These chains navigate the ribosomal exit tunnel, where they can form specific interactions with the ribosome and external molecules to regulate the rate of translation. Modern pharmacology has identified the nascent chain as a viable therapeutic target, particularly through the use of small molecules that induce selective translation arrest. For example, the drug PF-06446846 interacts with the nascent chain of PCSK9 within the ribosome to specifically stall its synthesis, providing a novel method for lowering cholesterol levels. Additionally, many macrolide antibiotics function by binding within the exit tunnel and obstructing the progression of the nascent polypeptide, thereby inhibiting bacterial protein production. Targeting the nascent chain offers a unique pathway for addressing diseases and modulating proteins previously considered undruggable by traditional inhibitors.

Other names

Nascent proteinNascent peptideRibosome-nascent chain complexRNCPeptidyl-tRNA complex

Selective translation stalling; Ribosomal exit tunnel obstruction; Induction of peptidyl-tRNA drop-off; Nonsense mutation read-through facilitation