| US 7,569,659 B1 | ||
| Admixture comprising a target molecule and a nucleic acid mimic comprising sterically bulky substituents | ||
| Leif Christensen, Charlottenlund (Denmark); Henrik Frydenlund Hansen, Radovre (Denmark); and Peter E. Nielsen, Hjortevaenget 509, 2980 Kokkedal (Denmark) | ||
| Assigned to Peter E. Nielsen, Federiksberg (Denmark) | ||
| Appl. No. 9/142,326 PCT Filed Mar. 07, 1997, PCT No. PCT/US97/03584 § 371(c)(1), (2), (4) Date Jan. 27, 1999, PCT Pub. No. WO97/32888, PCT Pub. Date Sep. 12, 1997. |
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| This patent is subject to a terminal disclaimer. | ||
| Int. Cl. C12Q 1/68 (2006.01); C07K 7/00 (2006.01) | ||
| U.S. Cl. 530—300 [536/23.1; 536/24.1; 536/24.3; 536/24.31; 536/24.32; 536/24.33; 536/25.3; 514/2; 514/44] | 11 Claims |
| 1. A nucleic acid mimic in admixture with at least one target molecule selected from the group consisting of nucleic acids,
transcription factors, carbohydrates and proteins, said mimic comprising a non-naturally occurring backbone structure to which
are appended a plurality of heterocyclic bases, at least one of said bases being substituted with at least one sterically
bulky substituent at a position one, two or three atoms removed from the position of attachment of said base to the backbone:
the nucleic acid mimic has formula (I):
 wherein:
n is at least 2,
each of L1-Ln is independently selected from the group consisting of hydrogen, hydroxy, (C1-C4)alkanoyl, naturally occurring nucleobases, non-naturally occurring nucleobases, aromatic moieties, DNA intercalators, nucleobase-binding
groups, heterocyclic moieties, and reporter ligands, at least one of L1-Ln being a naturally occurring nucleobase substituted with at least one sterically bulky substituent or non-naturally occurring
nucleobase substituted with at least one sterically bulky substituent;
each of C1-Cn is (CR6R7)y 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)alkylthio, NR3R4 and SR5, where R3 and R4 are hydrogen, a conjugate, (C1-C4)alkyl, hydroxy- or alkoxy- or alkylthio-substituted (C1-C4)alkyl, hydroxy, alkoxy, alkylthio or amino, and R5 is hydrogen, (C1-C6)alkyl, hydroxy-, alkoxy-, or alkylthio-substituted (C1-C6)alkyl, or R6 and R7 taken together complete an alicyclic or heterocyclic system;
each of D1-Dn is (CR6R7)z where R6 and R7 are as defined above;
each of y and z is zero or an integer from 1 to 10, the sum y+z being greater than 2 but not more than 10;
each of G1-Gn−1 is —NR3CO—, —NR3CS—, —NR3SO— or —NR3SO2—, in either orientation, where R3 is as defined above;
each pair of A1-An and B1-Bn are selected such that:
(a) A is a group of formula (IIa), (IIb) or (IIc) and B is N or R3N+; or
(b) A is a group of formula (IId) and B is CH;
 where:
X is O, S, Se, NR3, CH2 or C(CH3)2;
Y is a single bond, O, S or NR4;
each of p and q is zero or an integer from 1 to 5;
each of r and s is zero or an integer from 1 to 5;
each R1 and R2 is independently selected from the group consisting of hydrogen, (C1-C4)alkyl which may be hydroxy- or alkoxy- or alkylthio-substituted, hydroxy, alkoxy, alkylthio, amino and halogen;
each of G1-Gn−1 is —NR3CO—, —NR3CS—, —NR3SO— or —NR3SO2—, in either orientation, where R3 is as defined above;
Q is —CO2H, —CONR′R″, —SO3H or —SO2NR′R″ or an activated derivative of —CO2H or —SO3H; and
I is —NHR′″R″″ or —NR′″C(O)R″″, where R′, R″, R′″ and R″″ are independently selected from the group consisting of hydrogen,
alkyl, amino protecting groups, reporter ligands, intercalators, chelators, peptides, proteins, carbohydrates, lipids, steroids,
oligonucleotides, -LysNH2 and soluble and non-soluble polymers.
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