Peptide nucleic acid monomers and oligomers
Disclosed is a peptide nucleic acid monomer as well as a corresponding peptide nucleic acid molecule. The monomer comprises a terminal amino group and a terminal group A. The terminal amino group and the terminal group A are connected by an aliphatic moiety. The main chain of this aliphatic moiety is free of groups that are charged under physiological conditions. The terminal group A is one of —COOH, —COOR 3 , —COX, —COSR 3 , —CN, —CONH 2 , —CONHR 3 , —CONR 3 , R 4 , with R 3 and R4 being H or an aliphatic, alicyclic, aromatic, arylaliphatic or arylalicyclic group, and X being a halogen atom. The terminal amino group is substituted by an aliphatic group with a main chain of at least two carbon atoms and optionally 0 to about 2 heteroatoms selected from the group N, O, S, Se and Si. The main chain has a polar head group Z.
1. A peptide nucleic acid monomer
defined by the general structural formula (I):
wherein Q is an aliphatic bridge having a main chain of a length from 2 to 12 carbon atoms, optionally comprising 1 or 2 heteroatoms selected from N, O, S, Se and Si,
R 2 is one of a removable amino-protecting group, an aliphatic group, an alicyclic group, an aromatic group, an arylaliphatic group, an arylalicyclic group, a silyl-group or H,
A is one of —COOH, —COOR 3 , —COX, —COSR 3 , —CN, —CONH 2 , —CONHR 3 , or —CONR 3 R 4 , wherein R 3 , and in —CONR 3 R 4 R 4 , are independently selected from the group consisting of H, and an aliphatic, alicyclic, aromatic, arylaliphatic, and arylalicyclic group comprising 0 to 3 heteroatoms selected from N, O, S, Se and Si, and X in —COX is a halogen atom, and
E is a nucleobase, and
Z is a polar head group.
2. The peptide nucleic acid monomer of claim 1 , wherein the main chain of Q has a length from 4 to 8 carbon atoms.
3. The peptide nucleic acid monomer of claim 1 , wherein the peptide nucleic acid monomer is defined by the general structural formula (Ic):
wherein n is an integer from 2 to 12.
4. The peptide nucleic acid monomer of claim 3 , wherein n is selected in the range from 4 to 8.
5. The peptide nucleic acid monomer of claim 1 , wherein R 2 is one of a carbamate group, a methylaryl group (phtaloyl, tetrachlorophtaloyl), an acetamido group, a trifluoroacetamido group, an arylsulfonyl group (p-toluolsulfonyl-), an o-nitrophenylsulfenyl group, a trifluoroacetyl group-, a trityl group-, an allyl group, a 9-phenylfluorenyl group, a dithiasuccinyl group, a triazinanone group, an N-bis(methylthio)methylene group or an N-diphenylmethylene group.
6. The peptide nucleic acid monomer of claim 5 , wherein the carbamate is one of methoxycarbonyl-, ethoxycarbonyl-, benzylcarbonyl-, benzyloxycarbonyl-, nitrobenzyloxycarbonyl-, benzhydryloxycarbonyl-, allyloxycarbonyl-, tert-butoxycarbonyl-, 9-fluorenylmethoxycarbonyl-, 2-(trimethylsilyl)ethoxycarbonyl-, 2,2,2-tricholorethoxycarbonyl-, or 2-(4-trifluoromethylphenylsulfonyl)ethoxycarbonyl.
7. The peptide nucleic acid monomer of claim 1 , wherein the polar head group Z is capable of carrying a charge in aqueous solution in a pH range from about 5 to about 11.
8. The peptide nucleic acid monomer of claim 7 , wherein the polar head group Z is capable of carrying a positive charge in aqueous solution.
9. The peptide nucleic acid monomer of claim 8 , wherein the polar head group Z is capable of carrying a positive charge under physiological conditions.
10. The peptide nucleic acid monomer of claim 1 , wherein the polar head group Z is one of an amino group, an amido group, a carboxyl group, an ester group, a hydroxyl group, a thio group, a seleno group, a phosphonate group, a sulfonate group, a guanidine group or an imidazole group.
11. The peptide nucleic acid monomer of claim 1 , wherein the polar head group Z is an amino group or a guanidine group.
12. The peptide nucleic acid monomer of claim 1 , wherein the nucleobase is a purine base or a pyrimidine base.