Process for synthesizing cyclic peptide compound

摘要

The objective is to provide a novel process for synthesizing a cyclic peptide compound. It is also an objective to provide a novel cyclic peptide compound. The novel process for synthesizing a cyclic peptide compound comprises the steps of: (1) translationally synthesizing a non-cyclic peptide compound having in a molecule a functional group 1 and a functional group 2, which are a pair of functional groups capable of reacting to form a bond, and (2) cyclizing the non-cyclic peptide compound by the reaction of the functional groups 1 and 2 to form a bond. The novel cyclic peptide compound can be synthesized by the process.

主权项

1. A process for synthesizing a cyclic peptide compound, comprising the steps of:
(1) translationally synthesizing a non-cyclic peptide compound comprising non-natural amino acid(s), and containing a functional group 1 and a functional group 2, which are a pair of functional groups capable of reacting to form a bond; and (2) cyclizing the non-cyclic peptide compound by the reaction of the functional group 1 with the functional group 2 to form a bond between said groups, wherein a ribozyme capable of catalyzing an aminoacylation reaction of a tRNA with a moderately activated amino acid compound having an aromatic ring is used to translationally synthesize the non-cyclic peptide compound, and wherein the pair of functional groups 1 and 2 is one of the following pairs (A) to (C): wherein X1 is Cl or Br, and Ar is an aromatic ring optionally having a substituent, wherein the step (1) comprises the substeps of: (a) providing the ribozyme capable of catalyzing an aminoacylation reaction of a tRNA with a moderately activated amino acid compound having an aromatic ring; (b) providing an initiator tRNA and an amino acid compound having the functional group 1 for use as a substrate for the acylation reaction by the ribozyme; (c) performing an aminoacylation of the initiator tRNA with the amino acid compound having the functional group 1 using the ribozyme; (d) providing a cell-free translation system which contains at least an amino acid compound having the functional group 2 and a tRNA to be aminoacylated with the amino acid compound having the functional group 2, and is free of methionine; (e) providing a template DNA for forming an mRNA having at desired positions a codon corresponding to an anticodon of the initiator tRNA, and a codon corresponding to an anticodon of the tRNA to be aminoacylated with the amino acid compound having the functional group 2; and (f) adding the aminoacylated initiator tRNA obtained in the substep (c) and the template DNA to the cell-free translation system to synthesize the non-cyclic peptide compound.