Patent ID: 7087378

Claim:
A method for designing a specific polyamide XX 2 . . . X m -γ-X (m+1) . . . X (2m−1) X 2m -R 1 wherein X 1 , X 2 , X m , X (m+1) , X (2m−1) , and X 2m are carboxamide residues forming carboxamide binding pairs X 1 /X 2m , X 2 /X (2m−1) , X m /X (m+1); γ is γ-aminobutyric acid or 2,4 diaminobutyric acid, and R 1 is —NH(CH 2 ) 0-100 NR 2 R 3 , —NH(CH 2 ) 0-12 CONH(CH 2 ) 0-100 NR 2 R 3 , or —NHR 2 , where R 2 and R 3 are independently selected from the group consisting of H, Cl, NO, N-acetyl, benzyl, C 1-100 alky, C 1-100 alkylamine, C 1-100 alkyldiamine, C 1-100 alkylcarboxylate, C 1-100 alkenyl, a C 1-100 alkynyl, and C 1-100 alkyl-L, where L is selected from the group consisting of arylboronic acids, biotins, polyhistidines comprised from about 2 to 8 amino acids, haptens, solid phase supports, oligodeoxynucleotides, N-ethylnitrosourea, fluorescein, bromoacetamide, iodoacetamide, DL-α-lipoic acid, acridine, captothesin, pyrene, mitomycin, texas red, anthracene, anthrinilic acid, avidin, DAPI, and oligodeoxynucleotide, isosulfan blue, malachite green, psoralen, ethyl red, 4-(psoraen-8-yloxy)-butyrate, tartaric acid, and (+)-α-tocopheral, suitable for use as a DNA-binding ligand that is selective for identified target DNA-sequences 5′-WN 1 N 2 . . . N m W-3′ where m is an integer having a value from 3 to 6, the method comprising: (a) identifying a target sequence of double stranded DNA having the form 5′-WN 1 N 2 . . . N m W-3′,N 1 N 2 . . . N m being the sequence to be bound by carboxamide residues, wherein each N is independently chosen from the group A, G, C, and T, each W is independently chosen from the group A and T, and m is an integer having a value from 3 to 6; (b) representing the identified sequence as 5′-Wab . . . xW-3′, wherein a is a first nucleotide to be bound by the X 1 carboxamide residue, b is a second nucleotide to be bound by the X 2 carboxamide residue, and x is the corresponding nucleotide to be bound by the X m carboxamide residue; (c) defining a as A, G, C, or T to correspond to the first nucleotide to be bound by a carboxamide residue in the identified sequence; (d) selecting Im as the X 1 carboxamide residue and Py as the X 2m carboxamide residue if a=G; (e) selecting Py as the X 1 carboxamide residue and Im as the X 2m carboxamide residue if a=C; (f) selecting Hp as the X 1 carboxamide residue and Py as the X 2m carboxamide residue if a=T; (g) selecting Py as the X 1 carboxamide residue and Hp as the X 2m carboxamide residue if a=A; and (h) repeating steps c–g for b through x until all carboxamide residues are selected; wherein Im is N-methylimidazole, Hp is 3-hydroxy-N-methylpyrrole, Py is N-methylpyrrole, A is adenine, G is guanine, C is cytosine, and T is thymine; and synthesizing the polyamide.