US2003176325A1PendingUtilityA1

Modified peptide nucleic acid (PNA) molecules

Assignee: PANTHECO AS AND PETER E NIELSEPriority: Nov 11, 1998Filed: Oct 19, 2001Published: Sep 18, 2003
Est. expiryNov 11, 2018(expired)· nominal 20-yr term from priority
A61L 2/16A61L 2103/05A61K 47/62C12N 2310/3181C12N 15/113C12N 2310/152C12N 2310/323C12N 2310/3233C12N 2310/3513C12N 2310/33A61K 38/00
42
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Claims

Abstract

The present invention relates to novel drugs which may be used in combating infectious micro-organisms, particularly bacteria. More specifically, the invention relates to peptide nucleic acid (PNA) sequences that are modified by conjugating cationic peptides to the PNA moiety in order to obtain novel PNA molecules that exhibit enhanced anti-infective properties

Claims

exact text as granted — not AI-modified
We claim:  
     
         1 . A modified oligonucleotide having formula (III):  
       Peptide-L-Oligon  (III)  
       wherein L is a linker or a bond, Peptide is any amino acid sequence, and Oligon is an oligonucleotide or analog thereof.  
     
     
         2 . A composition comprising the modified oligonucleotide of  claim 1  or a pharmaceutically acceptable salt thereof.  
     
     
         3 . The composition of  claim 2  further comprising an antibiotic.  
     
     
         4 . The modified oligonucleotide of  claim 1  wherein L comprises at least one of the following: 8-amino-3,6-dioxaoctanoic acid (ADO), succinimidyl 4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC), 6-aminohexanoic acid (AHEX), 4-aminobutyric acid, 4-aminocyclohexylcarboxylic acid, polyethylene glycol, any amino acid, or any combination thereof.  
     
     
         5 . A modified peptide nucleic acid (PNA) molecule having formula (I):  
       Peptide-L-PNA  (I)  
       wherein L is a linker or a bond, Peptide is any amino acid sequence, and PNA is a peptide nucleic acid.  
     
     
         6 . The modified PNA molecule of  claim 5  wherein Peptide is a cationic peptide or peptide analog or a functionally similar moiety having formula (II):  
       C-(B-A) n -D,  (II)  
       wherein: 
 A is from 1 to 8 non-charged amino acids and/or amino acid analogs;  
 B is from 1 to 3 positively charged amino acids and/or amino acid analogs;  
 C is from 0 to 4 non-charged amino acids and/or amino acid analogs;  
 D is from 0 to 3 positively charged amino acids and/or amino acid analogs; and  
 n is 1-10;  
 wherein the total number of amino acids and/or amino acid analogs is from 3 to 20.  
 
     
     
         7 . The modified PNA molecule of  claim 5  wherein L comprises at least one of the following: 8-amino-3,6-dioxaoctanoic acid (ADO), succinimidyl 4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC), 6-aminohexanoic acid (AHEX), 4-aminobutyric acid, 4-aminocyclohexylcarboxylic acid, polyethylene glycol, any amino acid, or any combination thereof.  
     
     
         8 . The modified PNA molecule of  claim 7  wherein L comprises a combination of β.ALA or ADO and any one of SMCC, AHEX, 4-aminobutyric acid, 4-aminocyclohexylcarboxylic acid, polyethylene glycol, and any amino acid.  
     
     
         9 . The modified PNA molecule of  claim 8  wherein L is selected from the group consisting of: -achc-β.ala-, -achc-ado-, -lcsmcc-β.ala-, -mbs-β.ala-, -emcs-β.ala-, -lcsmcc-ado-, -mbs-ado-, -emcs-ado- or -smph-ado-.  
     
     
         10 . The modified PNA molecule of  claim 5  wherein A comprises from 1 to 6 non-charged amino acids and/or amino acid analogs and B comprises 1 or 2 positively charged amino acids and/or amino acid analogs.  
     
     
         11 . The modified PNA molecule of  claim 10  wherein A comprises from 1 to 4 non-charged amino acids and/or amino acid analogs.  
     
     
         12 . The modified PNA molecule of  claim 5  wherein the positively charged amino acids and amino acid analogs are selected from the group consisting of lysine, arginine, diamino butyric acid (DAB) and ornithine.  
     
     
         13 . The modified PNA molecule of  claim 5  wherein the non-charged amino acids and amino acid analogs are selected from the group consisting of Ala, Val, Leu, Ile, Pro, Phe, Trp, Met, Gly, Ser, Thr, Cys, Tyr, Asn, Gln and the non-naturally occurring amino acids 2-aminobutyric acid, β-cyclohexylalanine, 4-chlorophenylalanine, norleucine, and phenylglycine.  
     
     
         14 . The modified PNA molecule of  claim 5  wherein the non-charged amino acids and amino acid analogs are selected from the group consisting of Ala, Val, Leu, Ile, Pro, Phe, Trp, Met and the non-naturally occurring non-polar amino acids β-cyclohexylalanine, 4-chlorophenylalanine, and norleucine.  
     
     
         15 . The modified PNA molecule of  claim 5  wherein the total number of amino acids and/or amino acid analogs is 15 or less.  
     
     
         16 . The modified PNA molecule of  claim 5  wherein the total number of amino acids and/or amino acid analogs is 12 or less.  
     
     
         17 . The modified PNA molecule of  claim 5  wherein the total number of amino acids and/or amino acid analogs is 10 or less.  
     
     
         18 . The modified PNA molecule of  claim 5  wherein the Peptide is (KFF) 3 K (SEQ ID NO: 161) or subunits thereof comprising at least 3 amino acids.  
     
     
         19 . The modified PNA molecule of  claim 18  wherein the Peptide is (KFF) 3  (SEQ ID NO: 1.  
     
     
         20 . The modified PNA molecule of  claim 5  wherein the Peptide is selected from the group consisting of FFRFFRFFR (SEQ ID NO: 6), LLKLLKLLK (SEQ ID NO: 7), LLRLLRLLR (SEQ ID NO: 8), LLKKLAKAL (SEQ ID NO: 9), KFKVKFVVKK (SEQ ID NO: 1), LLKLLLKLLLK (SEQ ID NO: 12), LLKKLAKALK (SEQ ID NO: 13), RRLFPWWWPFRRVC (SEQ ID NO: 14), GRRWPWWPWKWPLIC (SEQ ID NO: 15), LVKKVATTLKKIFSKWKC (SEQ ID NO: 16), KKFKVKFVVKKC (SEQ ID NO: 17), and any subunit thereof comprising at least 3 amino acids, wherein at least one amino acid is a positively charged amino acid.  
     
     
         21 . A modified PNA molecule comprising:  
       
         
           
                 
                 
                 
               
                     
                 
                   H-KFFKFFKFFK-ado-CATAGCTGTTTC-NH 2 , 
                   (SEQ ID NO: 24) 
                     
                 
                     
                 
                   H-FFKFFKFFK-ado-CATAGCTGTTTC-NH 2 , 
                   (SEQ ID NO: 25) 
                 
                     
                 
                   H-FKFFKFFK-ado-CATAGCTGTTTC-NH 2 , 
                   (SEQ ID NO: 26) 
                 
                     
                 
                   H-KFFKLFFK-ado-CATAGCTGTTTC-NH 2 , 
                   (SEQ ID NO: 27) 
                 
                     
                 
                   H-FFKFFK-ado-CATAGCTGTTTC-NH 2 , 
                   (SEQ ID NO: 28) 
                 
                     
                 
                   H-FKFFK-ado-CATAGCTGTTTC-NH 2 , 
                   (SEQ ID NO: 29) 
                 
                     
                 
                   H-KFFK-ado-CATAGCTGTTTC-NH 2 , 
                   (SEQ ID NO: 30) 
                 
                     
                 
                   H-FFK-ado-CATAGCTGTTTC-NH 2 , 
                   (SEQ ID NO: 31) 
                 
                     
                 
                   H-FK-ado-CATAGCTGTTTC-NH 2 , 
                   (SEQ ID NO: 32) 
                 
                     
                 
                   H-K-ado-CATAGCTGTTTC-NH 2 , 
                   (SEQ ID NO: 33) 
                 
                     
                 
                   H-ado-CATAGCTGTTTC-NH 2 , 
                   (SEQ ID NO: 34) 
                 
                     
                 
                   H-KFFKFFKFF-ado-CATAGCTGTTTC-NH 2 , 
                   (SEQ ID NO: 35) 
                 
                     
                 
                   H-FFKFFKFF-ado-CATAGCTGTTTC-NH 2 , 
                   (SEQ ID NO: 36) 
                 
                     
                 
                   H-FKFFKFF-ado-CATAGCTGTTTC-NH 2 , 
                   (SEQ ID NO: 37) 
                 
                     
                 
                   H-KFFKFF-ado-CATAGCTGTTTC-NH 2 , 
                   (SEQ ID NO: 38) 
                 
                     
                 
                   H-FFKFF-ado-CATAGCTGTTTC-NH 2 , 
                   (SEQ ID NO: 39) 
                 
                     
                 
                   H-FKFF-ado-CATAGCTGTTTC-NH 2 , 
                   (SEQ ID NO: 40) 
                 
                     
                 
                   H-KFF-ado-CATAGCTGTTTC-NH 2 , 
                   (SEQ ID NO: 41) 
                 
                     
                 
                   H-FF-ado-CATAGCTGTTTC-NH 2 , 
                   (SEQ ID NO: 42) 
                 
                     
                 
                   H-F-ado-CATAGCTGTTTC-NH 2 , 
                   (SEQ ID NO: 43) 
                 
                     
                 
                   H-KFFKFFKFFK-ado-TTC AAA CAT AGT-NH 2 , 
                   (SEQ ID NO: 18) 
                 
                     
                 
                   H-KFFKFFKFFK-ado-TGA CTA GAT GAG-NH 2 , 
                   (SEQ ID NO: 44) 
                 
                     
                 
                   H-KFFKFFKFFK-ado-CCA TCT AAT CCT-NH 2 , 
                   (SEQ ID NO: 45) 
                 
                     
                 
                   H-FFKFFKFFK-GGC-smcc-ado-TTC AAA CAT AGT-NH 2 , 
                   (SEQ ID NO: 53) 
                 
                     
                 
                   H-FFRFFRFFR-GGC-smcc-ado-TTC AAA CAT AGT-NH 2 , 
                   (SEQ ID NO: 54) 
                 
                     
                 
                   H-LLKLLKLLK-GGC-Smcc-ado-TTC AAA CAT AGT-NH 2 , 
                   (SEQ ID NO: 55) 
                 
                     
                 
                   H-LLRLLRLLR-GGC-smcc-ado-TTC AAA CAT AGT-NH 2 , 
                   (SEQ ID NO: 56) 
                 
                     
                 
                   H-LLKKLAKALK-GC-smcc-ado-TTC AAA CAT AGT-NH 2 , 
                   (SEQ ID NO: 57) 
                 
                     
                 
                   H-KRRWPWWPWKK-C-smcc-ado-TTC AAA CAT AGT-NH 2 , 
                   (SEQ ID NO: 58) 
                 
                     
                 
                   H-KFKVKFVVKK-GC-smcc-ado-TTC AAA CAT AGT-NH 2 , 
                   (SEQ ID NO: 59) 
                 
                     
                 
                   H-LLKLLLKLLLK-C-smcc-ado-TTC AAA CAT AGT-NH 2 , 
                   (SEQ ID NO: 60) 
                 
                     
                 
                   H-FFKFFKFFK-GGC-Smcc-ado-TTC AAA CAT AGT-NH 2 , 
                   (SEQ ID NO: 61) 
                 
                     
                 
                   H-KFFKFFKFFK-C-smcc-ado-TTC AAA CAT AGT-NH 2 , 
                   (SEQ ID NO: 62) 
                 
                     
                 
                   H-F-ado-CCA TCT AAT CCT-NH 2 , 
                   (SEQ ID NO: 63) 
                 
                     
                 
                   H-FF-ado-CCA TCT AAT CCT-NH 2 , 
                   (SEQ ID NO: 64) 
                 
                     
                 
                   H-KFF-ado-CCA TCT AAT CCT-NH 2 , 
                   (SEQ ID NO: 65) 
                 
                     
                 
                   H-FKFF-ado-CCA TCT AAT CCT-NH 2 , 
                   (SEQ ID NO: 66) 
                 
                     
                 
                   H-FFKFF-ado-CCA TCT AAT CCT-NH 2 , 
                   (SEQ ID NO: 67) 
                 
                     
                 
                   H-KFFKFF-ado-CCA TCT AAT CCT-NH 2 , 
                   (SEQ ID NO: 68) 
                 
                     
                 
                   H-FKFFKFF-ado-CCA TCT AAT CCT-NH 2 , 
                   (SEQ ID NO: 69) 
                 
                     
                 
                   H-FFKFFKFF-ado-CCA TCT AAT CCT-NH 2 , 
                   (SEQ ID NO: 70) 
                 
                     
                 
                   H-KFFKFFKFF-ado-CCA TCT AAT CCT-NH 2 , 
                   (SEQ ID NO: 71) 
                 
                     
                 
                   H-LLKKLAKALKG-ahex-ado-CCA TCT AAT CCT-NH 2 , 
                   (SEQ ID NO: 21) 
                 
                     
                 
                   H-LLKKLAKALKG-ado-ado-CCA TCT AAT CCT-NH 2 , 
                   (SEQ ID NO: 72) 
                 
                     
                 
                   H-KFFKFFKFFK-ado-ado-CCA TCT AAT CCT-NH 2 , 
                   (SEQ ID NO: 73) 
                 
                     
                 
                   H-KFFKFFKFFK-ahex-ado-CCA TCT AAT CCT-NH 2 , 
                   (SEQ JD NO: 74) 
                 
                     
                 
                   H 2 N-KFFKFFKFFK-C-smcc-ado-CCA TCT AAT CCT-NH 2 , 
                   (SEQ ID NO: 75) 
                 
                     
                 
                   H 2 N-LLKKLAKALK-GC-smcc-ado-CCA TCT AAT CCT-NH 2 , 
                   (SEQ ID NO: 76) 
                 
                     
                 
                   H 2 N-KFFKFF-C-smcc-ado-CCA TCT AAT CCT-NH 2 , 
                   (SEQ ID NO: 77) 
                 
                     
                 
                   H-ado-TTC AAA CAT AGT-NH 2 , 
                   (SEQ ID NO: 78) 
                 
                     
                 
                   H 2 N-KFFKVKFVVKK-C-smcc-ado-TTC AAA CAT AGT-NH 2 , 
                   (SEQ ID NO: 79) 
                 
                     
                 
                   H 2 N-KFFKVKFVVKK-C-smcc-ado-TTG TGC CCC GTC-NH 2 , 
                   (SEQ ID NO: 80) 
                 
                     
                 
                   H 2 N-KKFKVKFVVKKC-achc-β.ala-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 81) 
                 
                     
                 
                   H-KFFKFFKFFK-achc-β.ala-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 82) 
                 
                     
                 
                   H 2 N-KKFKVKFVVKKC-lcsmcc-ado-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 83) 
                 
                     
                 
                   H 2 N-KKFKVKFVVKKC-mbs-ado-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 84) 
                 
                     
                 
                   H 2 N-KKFKVKFVVKKC-emcs-ado-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 85) 
                 
                     
                 
                   H 2 N-KKFKVKFVVKKC-smph-ado-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 86) 
                 
                     
                 
                   H 2 N-KKFKVKFVVKKC-amas-ado-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 87) 
                 
                     
                 
                   H 2 N-KKFKVKFVVKKC-smpb-ado-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 88) 
                 
                     
                 
                   H 2 N-KKFKVKFVVKKC-lcsmcc-gly-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 89) 
                 
                     
                 
                   H 2 N-KKFKVKFVVKKC-lcsmcc-β.ala-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 90) 
                 
                     
                 
                   H 2 N-KKFKVKFVVKKC-lcsmcc-β.cypr-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 91) 
                 
                     
                 
                   H 2 N-KKFKVKFVVKKC-lcsmcc-aha-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 92) 
                 
                     
                 
                   H 2 N-KKFKVKFVVKKC-Icsmcc-adc-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 93) 
                 
                     
                 
                   H-KFFKFFKFFK-ado-ado-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 94) 
                 
                     
                 
                   H-KFFKFFKFFK-ado-Gly-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 95) 
                 
                     
                 
                   H-KFFKFFKFFK-ado-P-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 96) 
                 
                     
                 
                   H-KFFKFFKFFK-ado-aha-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 97) 
                 
                     
                 
                   H-KFFKFFKFFK-ado-β.ala-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 98) 
                 
                     
                 
                   H-KFFKFFKFFK-ado-achc-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 99) 
                 
                     
                 
                   H-KFFKFFKFFK-Gly-ado-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 100) 
                 
                     
                 
                   H-KFFKFFKFFK-Gly-Gly-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 101) 
                 
                     
                 
                   H-KFFKFFKFFK-Gly-P-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 102) 
                 
                     
                 
                   H-KFFKFFKFFK-Gly-aha-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 103) 
                 
                     
                 
                   H-KFFKFFKFFK-Gly-β.ala-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 104) 
                 
                     
                 
                   H-KFFKFFKFFK-Gly-achc-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 105) 
                 
                     
                 
                   H-KFFKFFKFFK-P-ado-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 106) 
                 
                     
                 
                   H-KFFKFFKFFK-P-Gly-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 107) 
                 
                     
                 
                   H-KFFKFFKFFK-P-P-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 108) 
                 
                     
                 
                   H-KFFKFFKFFK-P-aha-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 109) 
                 
                     
                 
                   H-KFFKFFKFFK-P-β.ala-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 110) 
                 
                     
                 
                   H-KFFKFFKFFK-P-achc-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 111) 
                 
                     
                 
                   H-KFFKFFKFFK-aha-ado-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 112) 
                 
                     
                 
                   H-KFFKFFKFFK-aha-Gly-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 113) 
                 
                     
                 
                   H-KFFKFFKFFK-aha-P-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 114) 
                 
                     
                 
                   H-KFFKFFKFFK-aha-aha-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 115) 
                 
                     
                 
                   H-KFFKFFKFFK-aha-β.ala-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 116) 
                 
                     
                 
                   H-KFFKFFKFFK-aha-achc-TTCAAACATAGTNH 2 , 
                   (SEQ ID NO: 117) 
                 
                     
                 
                   H-KFFKFFKFFK-β.ala-ado-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 118) 
                 
                     
                 
                   H-KFFKFFKFFK-β.ala-Gly-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 119) 
                 
                     
                 
                   H-KFFKFFKFFK-β.ala-P-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 120) 
                 
                     
                 
                   H-KFFKFFKFFK-β.ala-aha-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 121) 
                 
                     
                 
                   H-KFFKFFKFFK-β.ala-β.ala-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 122) 
                 
                     
                 
                   H-KFFKFFKFFK-β.ala-achc-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 123) 
                 
                     
                 
                   H-KFFKFFKFFK-P-p-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 124) 
                 
                     
                 
                   H-KFFKFFKFFK-P-P-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 125) 
                 
                     
                 
                   H-KFFKFFKFFK-K-K-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 126) 
                 
                     
                 
                   H-KFFKFFKFFK-F-F-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 127) 
                 
                     
                 
                   H-KFFKFFKFFK-F-K-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 128) 
                 
                     
                 
                   H-KFFKFFKFFK-K-F-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 129) 
                 
                     
                 
                   H-KFFKFFKFFK-phg-ado-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 130) 
                 
                     
                 
                   H-KFFKFFKFFK-phg-Gly-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 131) 
                 
                     
                 
                   H-KFFKFFKFFK-phg-P-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 132) 
                 
                     
                 
                   H-KFFKFFKFFK-phg-aha-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 133) 
                 
                     
                 
                   H-KFFKFFKFFK-phg-β.ala-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 134) 
                 
                     
                 
                   H-KFFKFFKFFK-phg-achc-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 135) 
                 
                     
                 
                   H-KFFKFFKFFK-achc-ado-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 136) 
                 
                     
                 
                   H-KFFKFFKFFK-achc-Gly-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 137) 
                 
                     
                 
                   H-KFFKFFKFFK-achc-P-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 138) 
                 
                     
                 
                   H-KFFKFFKFFK-achc-aha-TTCAAACATAGT-NH 2 , 
                   (SEQ ID NO: 139) 
                 
                     
                 
                   H-KFFKFFKFFK-achc-β.ala-TTCAAACATAGT-NH 2 , or 
                   (SEQ ID NO: 140) 
                 
                     
                 
                   H-KFFKFFKFFK-achc-achc-TTCAAACATAGT-NH 2 . 
                   (SEQ ID NO: 141) 
                 
                     
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         22 . The modified PNA molecule of  claim 5  wherein the PNA sequence is complementary to at least one nucleotide sequence in a bacterium.  
     
     
         23 . The modified PNA molecule of  claim 22  wherein the PNA sequence is complementary to at least one ribosomal RNA sequence, messenger RNA sequence, or DNA sequence in said bacterium.  
     
     
         24 . The modified PNA molecule of  claim 5  wherein the PNA sequence is in a parallel or anti-parallel orientation.  
     
     
         25 . The modified PNA of  claim 22  wherein said at least one nucleotide sequence is essential for the survival of said bacterium and said PNA sequence inhibits the function of said at least one nucleotide sequence.  
     
     
         26 . The modified PNA molecule of  claim 5  wherein said PNA sequence comprises from 5 to 20 nucleobases.  
     
     
         27 . The modified PNA molecule of  claim 5  wherein said PNA sequence comprises from 7 to 15 nucleobases.  
     
     
         28 . The modified PNA molecule of  claim 5  wherein said PNA sequence comprises from 8 to 12 nucleobases.  
     
     
         29 . A modified PNA molecule comprising:  
       
         
           
                 
                 
                 
               
                     
                 
                   H-KFFKFFKFF-ado-JTJTJJT-ado-ado-ado-TCCCTCTC-Lys-NH 2 , 
                   (SEQ ID NO: 22) 
                     
                 
                     
                 
                   H-KFF-ado-JTJTJJT-ado-ado-ado-TCCTCTC-Lys-NH 2 , 
                   (SEQ ID NO: 46) 
                 
                     
                 
                   H-FKFF-ado-JTJTJJT-ado-ado-ado-TCCTCTC-Lys-NH 2 , 
                   (SEQ ID NO: 47) 
                 
                     
                 
                   H-FFKFF-ado-JTJTJJT-ado-ado-ado-TCCTCTC-Lys-NH 2 , 
                   (SEQ ID NO: 48) 
                 
                     
                 
                   H-KFFKFF-ado-JTJTJJT-ado-ado-ado-TCCTCTC-Lys-NH 2 , 
                   (SEQ ID NO: 49) 
                 
                     
                 
                   H-FKFFKFF-ado-JTJTJJT-ado-ado-ado-TCCTCTC-Lys-NH 2 , 
                   (SEQ ID NO: 50) 
                 
                     
                 
                   H-FFKFFKFF-ado-JTJTJJT-ado-ado-ado-TCCTCTC-Lys-NH 2 , or 
                   (SEQ ID NO: 51) 
                 
                     
                 
                   H-KFFKFFKFF-ado-JTJTJJT-ado-ado-ado-TCCTCTC-Lys-NH 2 . 
                   (SEQ ID NO: 52) 
                 
                     
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         30 . A composition comprising the modified PNA molecule of  claim 5  or a pharmaceutically acceptable salt thereof.  
     
     
         31 . The composition of  claim 30  further comprising an antibiotic.  
     
     
         32 . A composition comprising two or more modified PNA molecules of  claim 5  or pharmaceutically acceptable salts thereof.  
     
     
         33 . The composition of  claim 32  further comprising an antibiotic.  
     
     
         34 . A method of treating an infectious disease in a mammal comprising administering an effective amount of a modified PNA molecule of  claim 5  to said mammal.  
     
     
         35 . The method of  claim 34  wherein said infectious disease is a bacterial infection.  
     
     
         36 . A method of treating an infectious disease in a mammal comprising administering an effective amount of modified oligonucleotide of  claim 1  to said mammal.  
     
     
         37 . The method of  claim 36  wherein said infectious disease is a bacterial infection.  
     
     
         38 . A method of treating an infectious disease in a mammal comprising administering an effective amount of a composition of  claim 30  to said mammal.  
     
     
         39 . A method of treating an infectious disease in a mammal comprising administering an effective amount of a composition of  claim 32  to said mammal.  
     
     
         40 . A method of identifying a PNA sequence in a PNA molecule useful for inhibiting or reducing growth of at least one bacterium comprising: 
 contacting a first bacterium with a first modified PNA molecule of  claim 5  having a first PNA sequence, wherein said PNA sequence is complementary to at least one nucleotide sequence in said first bacterium;    contacting a second bacterium with a second modified PNA molecule of  claim 5  having a second PNA sequence, wherein said PNA sequence is complementary to at least one nucleotide sequence in said second bacterium; and    identifying which PNA sequence is more effective in inhibiting or reducing growth of said bacterium.    
     
     
         41 . The method of  claim 40  wherein said first and second PNA molecules are identical except for said PNA sequence, and said first and second bacterium are the same species.  
     
     
         42 . A method for disinfecting a non-living object comprising contacting said object with a modified oligonucleotide of  claim 1 .  
     
     
         43 . A method for disinfecting a non-living object comprising contacting said object with a modified PNA molecule of  claim 5 .  
     
     
         44 . A method for disinfecting a non-living object comprising contacting said object with a composition comprising a modified oligonucleotide of  claim 1 .  
     
     
         45 . A method for disinfecting a non-living object comprising contacting said object with a composition comprising a modified PNA molecule of  claim 5 .  
     
     
         46 . The method of  claim 42  wherein said object is a surgery tool, hospital inventory, dental tool, slaughterhouse inventory, slaughterhouse tool, dairy inventory, or dairy tool.  
     
     
         47 . The method of  claim 43  wherein said object is a surgery tool, hospital inventory, dental tool, slaughterhouse inventory, slaughterhouse tool, dairy inventory, or dairy tool.

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