DNA-based aptamers for human cathepsin G

Abstract

The present research is directed to the identification of non-peptidic inhibitors of cathepsin G characterised by high levels of selectivity and which can be efficaciously used in the treatment and prophylaxis of inflammatory occurrences and procoagulant conditions. The cathepsin G-inhibiting aptamers according to the invention consist of linear DNA or polynucleotide sequences having a chain length of at least 60 nucleotides and being substantially not subjected to undergo efficient base pairing.

1 . Cathepsin G-inhibiting aptamers consisting of linear DNA or polynucleotide sequences having a chain length of 70÷120 nucleotides and undergoing inter and/or intra molecular base pairing to an extent lower than 20%, said sequences being characterized by: 
 having a molar ratio AG/TC of 1.0÷2.0; or    being (GT) n  or (AC) n  oligopolymers in which n is in the range from 35 to 60; or    being (T) n  or (G) n  or (A) n  or (C) n  or (Inosine) n  omopolymers in which n is in the range from 70 to 120.    
     
     
         2 . Cathepsin G-inhibiting aptamers according to  claim 1  characterized by having a chain length of 70÷110 nucleotides.  
     
     
         3 . Cathepsin G-inhibiting aptamers according to  claim 1  characterized by having a chain length of 80÷100 nucleotides.  
     
     
         4 . Cathepsin G-inhibiting aptamers according to  claim 1  characterized by the fact of being single stranded sequences.  
     
     
         5 . Cathepsin G-inhibiting aptamers according to  claim 1  characterized by having a molar ratio AG/TC of 1.2÷1.8.  
     
     
         6 . Cathepsin G-inhibiting aptamers according to  claim 1  characterized by having a molar content in guanine of 25÷50%.  
     
     
         7 . Cathepsin G-inhibiting aptamers according to  claim 1  characterized by having a molar content in guanine of 35÷45%.  
     
     
         8 . Cathepsin G-inhibiting aptamers according to  claim 1  characterized by being (GT) n  or (AC) n  oligopolymers in which n is in the range from 40 to 50.  
     
     
         9 . Cathepsin G-inhibiting aptamers according to  claim 1  characterized by being (T) n  or (G) n  or (A) n  or (C) n  or (Inosine) n  omopolymers in which n is in the range from 80 to 100.  
     
     
         10 . Cathepsin G-inhibiting aptamers according to  claim 1  characterized by undergoing inter and/or intra molecular base pairing to an extent lower than 10%.  
     
     
         11 . Cathepsin G-inhibiting aptamers according to  claim 1  characterized by undergoing inter and/or intra molecular base pairing to an extent lower than 5%.  
     
     
         12 . A method for the treatment and prophylaxis of inflammatory occurrences, procoagulant conditions, genetic diseases, degenerative diseases, DNA damages, neoplasia and/or skin diseases wherein cathepsin G-inhibiting aptamers according to  claim 1  are administered to a patient in need of such a treatment.  
     
     
         13 . A pharmaceutical composition containing at least one cathepsin G-inhibiting aptamer according to  claim 1  together with customary eccipients and/or adjuvants.