Production method for noncyclic peptide-nucleic acid complex having, at n-terminal, amino acid with thiol group near amino group, library thereof, and cyclic peptide-nucleic acid complex library derived from same

A compound represented by the following general formula (IA) or general formula (IIA):

• wherein,
• R1 is a thiol group-protecting group which can be ribosomally synthesized;
• R2 and R3 each independently are a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, an aralkyl group, or a cycloalkyl group, each of which is optionally substituted;
• or R2 and R3 form a ring together with atoms to which they are bonded;
• or R2 or R3 form a ring together with R4 and atoms to which they are bonded;
• with the proviso that when R2 forms an azido group (—N3) together with the N atom to which it is bonded and SP-1, the above-mentioned definition does not apply to R2;
• R4 represents an alkylene, an arylene, a heteroarylene, an alkylenearylene, an alkyleneheteroarylene, an arylenealkylene, or a heteroarylenealkylene, each of which is optionally substituted;
• R11 and R12 each independently are a single bond, an alkylene, an arylene, a heteroarylene, an alkylene arylene, an alkyleneheteroarylene, an arylenealkylene, or a heteroarylenealkylene, each of which is optionally substituted;
• SP-1 forms an azido group together with the N atom to which it is bonded and R2, or is an amino group-protecting group represented by the following formula:
• wherein,
• P1 is a single bond, an arylene, or a heteroarylene,
• or represented by the following formula:
• wherein,
• P2 is an alkyl, an aryl, or a heteroaryl.

A compound represented by the following general formula (TB) or general formula:

• wherein,
• R1 is a thiol group-protecting group which can be ribosomally synthesized;
• R2 and R3 each independently are a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, an aralkyl group, or a cycloalkyl group, each of which is optionally substituted;
• or R2 and R3 form a ring together with atoms to which they are bonded;
• or R2 or R3 form a ring together with R4 and atoms to which they are bonded;
• with the proviso that when R2 forms an azido group (—N3) together with the N atom to which it is bonded and SP-1, the above-mentioned definition does not apply to R2;
• R4 represents an alkylene, an arylene, a heteroarylene, an alkylenearylene, an alkyleneheteroarylene, an arylenealkylene, or a heteroarylenealkylene, each of which is optionally substituted;
• R11 and R12 each independently are a single bond, an alkylene, an arylene, a heteroarylene, an alkylene arylene, an alkyleneheteroarylene, an arylenealkylene, or a heteroarylenealkylene, each of which is optionally substituted;
• SP-1 forms an azido group together with the N atom to which it is bonded and R2, or is an amino group-protecting group represented by the following formula:
• wherein,
• P1 is a single bond, an arylene, or a heteroarylene,
• or represented by the following formula:
• wherein,
• P2 is an alkyl, an aryl, or a heteroaryl;
• and R30 represents H or a hydroxyl group.

A noncyclic peptide or a complex of the peptide and a nucleic acid, wherein the peptide comprises at its N terminus an amino acid residue represented by general formula (I) or general formula (II) shown below comprising a first reaction point, and which comprises at a position at least four residues apart from the N terminus to the C-terminal side an amino acid residue comprising a second reaction point in one of its side chains:

• wherein,
• R1 is a thiol group-protecting group which can be ribosomally synthesized;
• R2 and R3 each independently are a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, an aralkyl group, or a cycloalkyl group, each of which is optionally substituted;
• or R2 and R3 form a ring together with atoms to which they are bonded;
• or R2 or R3 form a ring together with R4 and atoms to which they are bonded;
• with the proviso that when R2 forms an azido group (—N3) together with the N atom to which it is bonded and SP-1, the above-mentioned definition does not apply to R2;
• R4 represents an alkylene, an arylene, a heteroarylene, an alkylenearylene, an alkyleneheteroarylene, an arylenealkylene, or a heteroarylenealkylene, each of which is optionally substituted;
• R11 and R12 each independently are a single bond, an alkylene, an arylene, a heteroarylene, an alkylene arylene, an alkyleneheteroarylene, an arylenealkylene, or a heteroarylenealkylene, each of which is optionally substituted;
• SP-1 forms an azido group together with the N atom to which it is bonded and R2, or is an amino group-protecting group represented by the following formula:
• wherein,
• P1 is a single bond, an arylene, or a heteroarylene,
• or represented by the following formula:
• wherein,
• P2 is an alkyl, an aryl, or a heteroaryl.