Modified peptide nucleic acids

An oligomeric compound of formula I wherein:

• T1 is hydrogen, an amino protecting group, —C(O)R5, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C2-C10 alkenyl, substituted or unsubstituted C2-C10 alkynyl, alkylsulfonyl, arylsulfonyl, a chemical functional group, a reporter group, a conjugate group, a D or L α-amino acid linked via the α-carboxyl group or optionally through the ω-carboxyl group when the amino acid is aspartic acid or glutamic acid or a peptide derived from D, L or mixed D and L amino acids linked through a carboxyl group, wherein the substituent groups are selected from hydroxyl, amino, alkoxy, carboxy, benzyl, phenyl, nitro, thiol, thioalkoxy, halogen, alkyl, aryl, alkenyl and alkynyl;
• T2 is —OH, —N(Z1)Z2, R5, D or L α-amino acid linked via the α-amino group or optionally through the ω-amino group when the amino acid is lysine or ornithine or a peptide derived from D, L or mixed D and L amino acids linked through an amino group, a chemical functional group, a reporter group or a conjugate group;
• nn is from 2 to about 50;
• each Bx is, independently, an optionally protected heterocyclic base moiety;
• wherein at least one of said heterocyclic base moieties has one of formulas V or VI:
• 90
• wherein:
• R2 is hydrogen and R3 is Z1, —C(═J)—N(H)Z1, —C(═O)—(CH2)n—N(H)Z1, —C(═O)—(CH2)n—L—Z9, —(CH2)n—N(H)Z1, —(CH2)n—N(Z1)—(CH2)n—N(H)Z1, —(CH2)n—N(H)—C(═J)—N(H)Z3 or —(CH2)n—C(═NH)—N(H)Z3;
• or R3 is hydrogen and R2 is —C≡C—R4 or —(CH2)m—R4;
• L is O or S;
• J is O, S or NH;
• m is from 2 to 6;
• each n is from 1 to 6;
• R4 is H, C1-C6 alkyl, —CH2OH, —CH2—O—Q6, —CH2—N(H)—C(═O)—CF3, —CH2—N(H)Z1, —CH2—N(H)Z2, —C(═O)—Z4, —C(═O)—N(H)—(CH2)n—Q5, —CH2—N(H)—C(═O)—(CH2)nQ5 or —CH2—O—N(H)—C(═O)—(CH2)n—Q5;
• Q5is —L—Z3, —N(H)Z1, —C(═NH)—N(H)Z3, —N(H)—C(═J) N(H)Z3 or —N(Z1)—(CH2)n—N(H)Z1;
• Q6 is —N(H)Z1, —N(H)Z2, benzyl, benzoyl, —C(═O)—(CH2)n—CH3 or phthalimido;
• Z1 is hydrogen, C1-C6 alkyl, or an amino protecting group;
• Z2 is hydrogen, C1-C6 alkyl, an amino protecting group, —C(═O)—(CH2)n—J—Z3, a D or L α-amino acid linked via the α-carboxyl group or optionally through the ω-carboxyl group when the amino acid is aspartic acid or glutamic acid or a peptide derived from D, L or mixed D and L amino acids linked through a carboxyl group;
• Z3 is hydrogen, an amino protecting group, —C1-C6 alkyl, —C(═O)—CH3, benzyl, benzoyl, or —(CH2)n—N(H)Z1;
• Z4 is —OH, C1-C6 alkyl, benzyl, —N(H)Z1, a D or L α-amino acid linked via the α-amino group or optionally through the ω-amino group when the amino acid is lysine or ornithing or a peptide derived from D, L or mixed D and L amino acids linked through an amino group;
• Z9 is hydrogen, —C1-C6 alkyl, —C(═O)—CH3, benzyl or a D or L α-amino acid linked via the α-carboxyl group or optionally through the ω-carboxyl group when the amino acid is aspartic acid or glutamic acid or a peptide derived from D, L or mixed D and L amino acids linked through a carboxyl group;
• and
• each R5 is a carbonyl protecting group.

An oligomeric compound of formula I wherein:

• T1 is hydrogen, an amino protecting group, —C(O)R5, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C2-C10 alkenyl, substituted or unsubstituted C2-C10 alkynyl, alkylsulfonyl, arylsulfonyl, a chemical functional group, a reporter group, a conjugate group, a D or L α-amino acid linked via the α-carboxyl group or optionally through the ω-carboxyl group when the amino acid is aspartic acid or glutamic acid or a peptide derived from D, L or mixed D and L amino acids linked through a carboxyl group, wherein the substituent groups are selected from hydroxyl, amino, alkoxy, carboxy, benzyl, phenyl, nitro, thiol, thioalkoxy, halogen, alkyl, aryl, alkenyl and alkynyl;
• T2 is —OH, —N(Z1)Z2, R5, D or L α-amino acid linked via the α-amino group or optionally through the c-amino group when the amino acid is lysine or ornithine or a peptide derived from D, L or mixed D and L amino acids linked through an amino group, a chemical functional group, a reporter group or a conjugate group;
• nn is from 2 to about 50;
• each Bx is, independently, an optionally protected heterocyclic base moiety wherein at least one of said heterocyclic base moieties has formula VIII:
• 91
• wherein
• A10 is S;
• and A11 is CH2, O or S;
• or
• A10 is O and A11 is CH2;
• one of A12 and A13 is hydrogen and the other of A12 and A13 is a group of formula:
• 92
• wherein:
• G1 is —CN, —OA20, —SA20, —N(H)A20, —ON(H)A20 or —C(═NH)N(H)A20;
• G2 is H, —NHA20, —C(═O)N(H)A20, —C(═S)N(H)A20 or —C(═NH)N(H)A20,
• each G3 is, independently, H or an amino protecting group;
• A20 is H, a protecting group, substituted or unsubstituted C1-C10 alkyl, acetyl, benzyl, —(CH2)p3NH2, —(CH2)p3N(H)G3, a D or L α-amino acid, or a peptide derived from D, L or racemic ac-amino acids;
• each R5 is a carbonyl protecting group;
• each p1 is, independently, from 2 to about 6;
• p2 is from 1 to about 3;
• and
• p3 is from 1 to about 4.

An oligomeric compound of formula I wherein:

• T1 is hydrogen, an amino protecting group, —C(O)R5, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C2-C10 alkenyl, substituted or unsubstituted C2-C10 alkynyl, alkylsulfonyl, arylsulfonyl, a chemical functional group, a reporter group, a conjugate group, a D or L α-amino acid linked via the α-carboxyl group or optionally through the ()—carboxyl group when the amino acid is aspartic acid or glutamic acid or a peptide derived from D, L or mixed D and L amino acids linked through a carboxyl group, wherein the substituent groups are selected from hydroxyl, amino, alkoxy, carboxy, benzyl, phenyl, nitro, thiol, thioalkoxy, halogen, alkyl, aryl, alkenyl and alkynyl;
• T2 is —OH, —N(Z1)Z2, R5, D or L α-amino acid linked via the α-amino group or optionally through the ω-amino group when the amino acid is lysine or ornithine or a peptide derived from D, L or mixed D and L amino acids linked through an amino group, a chemical functional group, a reporter group or a conjugate group;
• nn is from 2 to about 50;
• each Bx is, independently, an optionally protected heterocyclic base moiety wherein at least one of said heterocyclic base moieties has formula XVI:
• 93
• wherein
• A15 is O or S;
• and
• A16 is selected from the group consisting of —O—(CH2)p1C(═NH)N(H)A20, —O—(CH2)p1N(H)—C(═O)N(H)A20 or —O—(CH2)p1N(H)—C(═S)N(H)A20 and A17 is H;
• or A16 is H and A17 is a group of formula:
• 94
• wherein:
• G1 is —CN, —OA20, —SA20, —N(H)A20, —ON(H)A20 or —C(═NH)N(H)A20;
• G2 is H, —NHA20, —C(═O)N(H)A20, —C(═S)N(H)A20 or —C(═NH)N(H)A20,
• each G3 is, independently, H or an amino protecting group;
• A20 is H, a protecting group, substituted or unsubstituted C1-C10 alkyl, acetyl, benzyl, —(CH2)p3N(H)G3, a D or L α-amino acid, or a peptide derived from D, L or racemic α-amino acids;
• each R5 is carbonyl protecting group;
• each p1 is from 2 to about 6;
• p2 is from 1 to about 3;
• and
• p3 is from 1 to about 4.

An oligomeric compound having one of formulas X, XI, XII, XIII, XIV or XV:

• 95 96
• wherein:
• T1 is hydrogen, an amino protecting group, —C(O)R5, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C2-C10 alkenyl, substituted or unsubstituted C2-C10 alkynyl, alkylsulfonyl, arylsulfonyl, a chemical functional group, a reporter group, a conjugate group, a D or L α-amino acid linked via the α-carboxyl group or optionally through the ω-carboxyl group when the amino acid is aspartic acid or glutamic acid or a peptide derived from D, L or mixed D and L amino acids linked through a carboxyl group, wherein the substituent groups are selected from hydroxyl, amino, alkoxy, carboxy, benzyl, phenyl, nitro, thiol, thioalkoxy, halogen, alkyl, aryl, alkenyl and alkynyl;
• T2 is —OH, —N(Z1)Z2, R5, D or L α-amino acid linked via the α-amino group or optionally through the ω-amino group when the amino acid is lysine or ornithine or a peptide derived from D, L or mixed D and L amino acids linked through an amino group, a chemical functional group, a reporter group or a conjugate group;
• nn is from 2 to about 50;
• each chiral ring carbon having an asterick (*) is prepared having R, S or mixed R and S configuration;
• each Bx is, independently, an optionally protected heterocyclic base moiety wherein at least one of said heterocyclic base moieties has one of formulas II or III:
• 97
• wherein:
• R1 is —CH2—Q2, —C≡C—Q2, —CH2(CH2)n—Q3, or —CH═CH—C(═O)—Q4;
• Q1 is —N3, —CN, —N(Z1)2, —N(Z1)—(CH2)n—C(═NH2)—N(H)—Z3, —N(Z1)—C(═J)—N(H)—Z5, —L—(CH2)n—C(═O)Z3, —L—(CH2)n—L—Z3, —L—(CH2)n—N(H)Z1, —L—(CH2)n—N(Z1)—(CH2)n—N(H)Z1, —L—(CH2)n—C(═NH)N(Z1)Z3 or —L—(CH2)n—N(Z1)—C(═J)—N(H)Z3;
• Q2 is H, C1-C6 alkyl, —C(═O)—N(H)Z1, —C(═O)—O—CH2—CH3, C(═O)—O—benzyl, —C(═O)—Z4, —CH2—O—Q6, —CH2—C(═NH)—N(H)—Z3, —CH2—N(H)—Z2,—CH2—N(H)—C(═O)—CF3, —CH2—N(H)Z1, —CH2—N(H)—C(═NH)—N(H)—Z3, —CH2—O—N(H)—C(═O)—(CH2)n—Q5, —C(═O)—N(H)—(CH2)n—Q5 or —CH2—N(H)—C(═O)—(CH2)n—Q5;
• Q3 is hydrogen, —O—C1-C6 alkyl, —N(H)—Z1, —N(H)—Z2, —N(H)—C(═O)—CF3, —N(H)—C(═NH)—N(H)Z1, —O—Q6, —N(H)—C(═O)—(CH2)n—Q5, —O—N(H)—C(═O)—(CH2)n—Q5, —C(═O)—N(H)—(CH2)n—Q5 or —C(═O)—Q7;
• Q4 is is Z4, —L—Z3, —N(H)Z3, —C(═NH)—N(H)Z3, —N(H)—C(═J) N(H)Z3, N(Z1)—(CH2)n—N(H)Z3, —C(═O)—N(H)—(CH2)n—C(═NH)—N(H)Z3, —C(═O)—N(H)—(CH2)n—N(H)—C(═J)—N(H)Z3 or —C(═O)—N(H)—(CH2)n—N(Z1)—(CH2)n—N(H)Z1;
• Q5 is —L—Z3, —N(H)Z3, —C(═NH)—N(H)Z3, —N(H)—C(═J) N(H)Z3 or N(Z1)—(CH2)n—N(H)Z3;
• Q6 is hydrogen, —N(H)Z1, —N(H)Z2, benzyl, benzoyl, —C(═O)—(CH2)n—H or phthalimido;
• Q7 is —OH, —O—C1-C6 alkyl, —O-benzyl, —Z4, —N(H)Z1,
• each L is O or S;
• each J is O, S or NH;
• each n is from 1 to 6;
• Z1 is hydrogen, C1-C6 alkyl, or an amino protecting group;
• Z2 is hydrogen, C1-C6 alkyl, an amino protecting group, —C(═O)—(CH2)n—J—Z3, a D or L α-amino acid linked via the α-carboxyl group or optionally through the ω-carboxyl group when the amino acid is aspartic acid or glutamic acid or a peptide derived from D, L or mixed D and L amino acids linked through a carboxyl group;
• Z3 is hydrogen, an amino protecting group, —C1-C6 alkyl, —C(═O)—CH3, benzyl, benzoyl, or —(CH2)n—N(H)Z1,;
• Z4 is a D or L α-amino acid linked via the α-amino group or optionally through the ω-amino group when the amino acid is lysine or ornithine or a peptide derived from D, L or mixed D and L amino acids linked through an amino group;
• Z5 is hydrogen, an amino protecting group or —C(═O)—(CH2)n—J—Z3;
• and
• each R5 is a carbonyl protecting group.

An oligomeric compound having one of formulas X, XI, XII, XIII, XIV or XV:

• 98 99
• wherein:
• T1 is hydrogen, an amino protecting group, —C(O)R5, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C2-C10 alkenyl, substituted or unsubstituted C2-C10 alkynyl, alkylsulfonyl, arylsulfonyl, a chemical functional group, a reporter group, a conjugate group, a D or L α-amino acid linked via the α-carboxyl group or optionally through the ω-carboxyl group when the amino acid is aspartic acid or glutamic acid or a peptide derived from D, L or mixed D and L amino acids linked through a carboxyl group, wherein the substituent groups are selected from hydroxyl, amino, alkoxy, carboxy, benzyl, phenyl, nitro, thiol, thioalkoxy, halogen, alkyl, aryl, alkenyl and alkynyl;
• T2 is —OH, —N(Z1)Z2, R5, D or L α-amino acid linked via the α-amino group or optionally through the ω-amino group when the amino acid is lysine or ornithine or a peptide derived from D, L or mixed D and L amino acids linked through an amino group, a chemical functional group, a reporter group or a conjugate group;
• nn is from 2 to about 50;
• each chiral ring carbon having an asterick (*) is prepared having R, S or mixed R and S configuration;
• each Bx is, independently, an optionally protected heterocyclic base moiety wherein at least one of said heterocyclic base moieties has one of formulas V or VI:
• 100
• wherein:
• R2 is hydrogen and R3 is Z1, —C(═J)—N(H)Z1, —C(═O)—(CH2)n—N(H)Z1, —C(═O)—(CH2)n—L—Z9, —(CH2)n—N(H)Z1, —(CH2)n—N(Z1)—(CH2)n—N(H)Z1, —(CH2)n—N(H)—C(═J)—N(H)Z3 or —(CH2)n—C(═NH)—N(H)Z3;
• or R3 is hydrogen and R2 is —C≡C—R4 or —(CH2)m—R4;
• L is O or S;
• J is O, S or NH;
• m is from 2 to 6;
• each n is from 1 to 6;
• R4 is H, C1-C6 alkyl, —CH2OH, —CH2—O—Q6, —CH2—N(H)—C(═O)—CF3, —CH2—N(H)Z1, —CH2—N(H)Z2, —C(═O)—Z4, —C(═O)—N(H)—(CH2)n—Q5, —CH2—N(H)—C(═O)—(CH2)nQ5 or —CH2—O—N(H)—C(═O)—(CH2)n—Q5;
• Q5 is —L—Z3, —N(H)Z1, —C(═NH)—N(H)Z3, —N(H)—C(═J) N(H)Z3 or —N(Z1)—(CH2)n—N(H)Z1;
• Q6 is —N(H)Z1, —N(H)Z2, benzyl, benzoyl, —C(═O)—(CH2)n—CH3 or phthalimido;
• Z1 is hydrogen, C1-C6 alkyl, or an amino protecting group;
• Z2 is hydrogen, C1-C6 alkyl, an amino protecting group, —C(═O)—(CH2)n—J—Z3, a D or L α-amino acid linked via the α-carboxyl group or optionally through the ω-carboxyl group when the amino acid is aspartic acid or glutamic acid or a peptide derived from D, L or mixed D and L amino acids linked through a carboxyl group;
• Z3 is hydrogen, an amino protecting group, —C1-C6 alkyl, —C(═O)—CH3, benzyl, benzoyl, or —(CH2)n—N(H)Z1;
• Z4 is —OH, C1-C6 alkyl, benzyl, —N(H)Z1, a D or L α-amino acid linked via the α-amino group or optionally through the ω-amino group when the amino acid is lysine or ornithing or a peptide derived from D, L or mixed D and L amino acids linked through an amino group;
• Z9 is hydrogen, —C1-C6 alkyl, —C(═O)—CH3, benzyl or a D or L α-amino acid linked via the α-carboxyl group or optionally through the ω-carboxyl group when the amino acid is aspartic acid or glutamic acid or a peptide derived from D, L or mixed D and L amino acids linked through a carboxyl group;
• and
• each R5 is a carbonyl protecting group.

An oligomeric compound having one of formulas X, XI, XII, XIII, XIV or XV:

• 101 102
• wherein:
• T1 is hydrogen, an amino protecting group, —C(O)R5, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C2-C10 alkenyl, substituted or unsubstituted C2-C10 alkynyl, alkylsulfonyl, arylsulfonyl, a chemical functional group, a reporter group, a conjugate group, a D or L α-amino acid linked via the α-carboxyl group or optionally through the ω-carboxyl group when the amino acid is aspartic acid or glutamic acid or a peptide derived from D, L or mixed D and L amino acids linked through a carboxyl group, wherein the substituent groups are selected from hydroxyl, amino, alkoxy, carboxy, benzyl, phenyl, nitro, thiol, thioalkoxy, halogen, alkyl, aryl, alkenyl and alkynyl;
• T2 is —OH, —N(Z1)Z2, R5, D or L α-amino acid linked via the α-amino group or optionally through the ω-amino group when the amino acid is lysine or ornithine or a peptide derived from D, L or mixed D and L amino acids linked through an amino group, a chemical functional group, a reporter group or a conjugate group;
• nn is from 2 to about 50;
• each chiral ring carbon having an asterick (*) is prepared having R, S or mixed R and S configuration;
• each Bx is, independently, an optionally protected heterocyclic base moiety wherein at least one of said heterocyclic base moieties has formula VIII:
• 103
• wherein
• A10 is O or S;
• A11 is CH2, N—CH3, O or S;
• each A12 and A13 is hydrogen or one of A12 and A13 is hydrogen and the other of A12 and A13 is a group of formula:
• 104
• wherein:
• G1 is —CN, —OA20, —SA20, —N(H)A20, —ON(H)A20 or —C(═NH)N(H)A20;
• G2 is H, —NHA20, —C(═O)N(H)A20, —C(═S)N(H)A20 or —C(═NH)N(H)A20, each G3 is, independently, H or an amino protecting group;
• A20 is H, a protecting group, substituted or unsubstituted C1-C10 alkyl, acetyl, benzyl, —(CH2)p3NH2, —(CH2)p3N(H)G3, a D or L α-amino acid, or a peptide derived from D, L or racemic α-amino acids;
• each R5 is a carbonyl protecting group;
• each p1 is, independently, from 2 to about 6;
• p2 is from 1 to about 3;
• and
• p3 is from 1 to about 4.