Synthetic procedures for peptide nucleic acids

A process for preparing a compound comprising a polyamide backbone bearing a plurality of ligands that are individually bound to aza nitrogen atoms located within said backbone, comprising the steps of:

• A) providing a polymer substrate, said polymer being functionalized with a chemical group capable of forming an anchoring linkage with an amino acid;
• B) coupling said polymer with a first amino acid through said anchoring linkage, said first amino acid having formula (IV):
• wherein:
• L is selected from the group consisting of naturally occurring nucleobases, non-naturally occurring nucleobases, provided that at least one L is a naturally occurring nucleobase;
• aromatic moieties, DNA intercalators, nucleobase-binding groups, heterocyclic moieties, and reporter ligands, wherein amino groups are, optionally, protected by amino protecting groups;
• provided that at least one L is a naturally occurring nucleobase;
• A is a single bond or a group of the formula:
• where:
• X is O, S, Se, NR3, CH2 or C(CH3)2;
• Y1 is a single bond, O, S or NR4;
• Y2 is single bond, O or S;
• p and q are zero or integers from 1 to 5;
• r and s are zero or integers from 1 to 5;
• R1 and R2 are independently selected from the group consisting of hydrogen, (C1-C4)alkyl, hydroxy- or alkoxy- or alkylthio-substituted (C1-C4)alkyl, hydroxy, alkoxy, alkylthio, amino and halogen;
• and
• R3 and R4 are independently selected from the group consisting of hydrogen, (C1-C4)alkyl, hydroxy- or alkoxy- or alkylthio-substituted (C1-C4)alkyl, hydroxy, alkoxy, alkylthio and amino;
• B is N or R3N+, where R3 is as defined above;
• T is CR6R7, CHR6CHR7 or CR6R7CH2, where R6 is hydrogen and R7 is selected from the group consisting of the side chains of naturally occurring alpha amino acids, or R6 and R7 are independently selected from the group consisting of hydrogen, (C2-C6)alkyl, aryl, aralkyl, heteroaryl, hydroxy, (C1-C6)alkoxy, (C1-C6)alkythio, NR3R4 and SR5, where R3 and R4 are as defined above, and R5 is hydrogen or (C1-C6)alkyl, hydroxy-, alkoxy-, or alkylthio-substituted (C1-C6)alkyl, or R6 and R7 taken together complete an alicyclic or heterocyclic system;
• D is CR6R7, CH2CR6R7 or CHR6CHR7, where R6 and R7 are as defined above;
• E is COOH or an activated or protected derivative thereof;
• and
• G is NPgR3 where R3 is as defined above and Pg is an amino protecting group;
• C) removing said amino protecting group from said coupled first amino acid to generate a free amino group;
• and
• D) reacting said free amino group with a second amino acid having formula (IV) to form said compound.