Novel compounds

Abstract

Spermine:peptide-based surfactant compounds are disclosed. The compounds are based on a spermine backbone with peptide groups and optionally hydrocarbyl groups linked thereto. Uses of the spermine:peptide-based surfactant compounds and methods for their production are also disclosed.

1 . A spermine:peptide-based surfactant compound having the general structure of formula (1):  
       
         
           
           
               
               
           
         
       
       where R 1  and R 3  are hydrogen and R 2  and R 4 , which may be the same or different, are peptide groups formed from one or more amino acids linked together, in a linear or branched manner, by amide (CONH) bonds and further linked to the spermine backbone by amide bonds, having the general formula (II):  
       
         
           
           
               
               
           
         
       
       where 
 p1 is 0 to 5 and p2 is 1 to 5; and the values for p3 and p4, which may be the same or different, are from 0 to 5;  
 A1, A3 and A4, which may be the same or different, are amino acids selected from serine, lysine, ornithine, threonine, histidine, cysteine, arginine and tyrosine; and  
 A2 is an amino acid selected from lysine, ornithine and histidine;  
 and R 5  and R 6  are saturated or unsaturated hydrocarbyl groups having up to 24 carbon atoms and linked to the spermine backbone by an amide or an amine (NCH 2 ) linkage; or  
 where R 1  and R 3  are hydrogen, R 2  and R 4 , which may be the same or different are saturated or unsaturated hydrocarbyl groups having up to 24 carbon atoms and linked to the spermine backbone by amide or amine bonds, and R 5  and R 6 , which may be the same or different, are peptide groups of formula (II) linked to the spermine backbone by amide bonds; or  
 a salt, preferably a pharmaceutically acceptable salt thereof.  
 
     
     
         2 . A spermine:peptide-based surfactant compound according to  claim 1  which is symmmetrical, that is R 1  and R 3  are the same, R 2  and R 4  are the same, and R 5  and R 6  are the same.  
     
     
         3 . A spermine:peptide-based surfactant compound according to  claim 1  or  2  wherein in the peptide group of formula (I) p1 is 1 and p2, p3 and p4 are all 0.  
     
     
         4 . A spermine:peptide-based surfactant compound according to  claim 1  or  2  wherein in the peptide group of formula (11) p 1 and p2 are both 1 and p3 and p4 are both 0.  
     
     
         5 . A spermine:peptide-based surfactant compound according to  claim 1  or  2  wherein in the peptide group of formula (I) p1 is 0 and p2, p3 and p4 are all 1.  
     
     
         6 . A spermine:peptide-based surfactant compound according to  claim 1  or  2  wherein in the peptide group of formula (I) p1 and p3 are 0, p2 is 1 and p4 is 2.  
     
     
         7 . A spermine:peptide-based surfactant compound according to any one of  claims 1  to  6  wherein the A1 is serine.  
     
     
         8 . A spermine:peptide-based surfactant compound according to any one of  claims 1  to  6  wherein the A2 is lysine.  
     
     
         9 . A spermine:peptide-based surfactant compound according to  claim 1  wherein the hydrocarbyl group is selected from: 
 —(CH 2 ) 11 CH 3      —(CH 2 ) 13 CH 3      —(CH 2 ) 15 CH 3      —(CH 2 ) 17 CH 3      —(CH 2 ) 19 CH 3      —(CH 2 ) 23 CH 3      —(CH 2 ) 8 CH═CH(CH 2 ) 5 CH 3      —(CH 2 ) 8 CH═CH(CH 2 ) 7 CH 3      —(CH 2 ) 8 CH═CHCH 2 CH═CH(CH 2 ) 4 CH 3      —(CH 2 ) 8 (CH═CHCH 2 ) 3 CH 3      —(CH 2 ) 4 CH═CH(CH 2 CH═CH) 3 (CH 2 ) 4 CH 3      —(CH 2 ) 8 CH═CH(CH 2 ) 5 CH 3  Trans    —(CH 2 ) 8 CH═CH(CH 2 ) 7 CH 3  Trans    —(CH 2 ) 9 CHCH 3 (CH 2 ) 7 CH 3      
     
     
         10 . A spermine:peptide-based surfactant compound according to  claim 1  wherein the hydrocarbyl group is selected from: 
 —CO(CH 2 ) 10 CH 3      —CO(CH 2 ) 12 CH 3      —CO(CH 2 ) 14 CH 3      —CO(CH 2 ) 16 CH 3      —CO(CH 2 ) 18 CH 3      —CO(CH 2 ) 22 CH 3      —CO(CH 2 ) 7 CH═CH(CH 2 ) 5 CH 3      —CO(CH 2 ) 7 CH═CH(CH 2 ) 7 CH 3      —CO(CH 2 ) 7 CH═CHCH 2 CH═CH(CH 2 ) 4 CH 3      —CO(CH 2 ) 7 (CH═CHCH 2 ) 3 CH 3      —CO(CH 2 ) 3 CH═CH(CH 2 CH═CH) 3 (CH 2 ) 4 CH 3      —CO(CH 2 ) 7 CH═CH(CH 2 ) 5 CH 3  Trans    —CO(CH 2 ) 7 CH═CH(CH 2 ) 7 CH 3  Trans    —CO(CH 2 ) 8 CHCH 3 (CH 2 ) 7 CH 3      —COCHOH(CH 2 ) 21 CH 3                           
     
     
         11 . The compound:  
       
         
           
           
               
               
           
         
       
     
     
         12 . The compound:  
       
         
           
           
               
               
           
         
       
     
     
         13 . The compound GSC1 of formula:  
       
         
           
           
               
               
           
         
       
     
     
         14 . The compound GSC4 of formula:  
       
         
           
           
               
               
           
         
       
     
     
         15 . The compound GSC40 of formula:  
       
         
           
           
               
               
           
         
       
     
     
         16 . The compound GSC42 of formula:  
       
         
           
           
               
               
           
         
       
     
     
         17 . The compound GSC2 of formula:  
       
         
           
           
               
               
           
         
       
     
     
         18 . The compound GSC12 of formula:  
       
         
           
           
               
               
           
         
       
     
     
         19 . The use of a spermine:peptide-based surfactant compound as defined in any one of  claims 1  to  15  in facilitating transfection of DNA or RNA polynucleotides or analogs thereof into a eukaryotic or prokaryotic cell in vivo or in vitro.  
     
     
         20 . The use of a spermine:peptide-based surfactant compound according to  claim 19  wherein the compound is used in combination with one or more supplements selected from the group consisting of: 
 (i) a neutral carrier; or    (ii) a complexing reagent.    
     
     
         21 . The use according to  claim 20  wherein the neutral carrier is dioleoyl phosphatidylethanolamine (DOPE).  
     
     
         22 . The use according to  claim 20  wherein the complexing reagent is PLUS reagent.  
     
     
         23 . The use according to  claim 20  wherein the complexing reagent is a peptide comprising mainly basic amino acids.  
     
     
         24 . The use according to  claim 23  wherein the peptide consists of basic amino acids.  
     
     
         25 . The use according to  claim 23  or  24  wherein the basic amino acids are selected from lysine and arginine.  
     
     
         26 . The use according to  claim 24  wherein the peptide is polylysine or polyornithine.  
     
     
         27 . The use according to any one of  claims 19  to  26  wherein the oligonucleotides or polynucleotides are transferred into cells to achieve an antisense knock-out effect.  
     
     
         28 . The use according to  claim 19  wherein the oligonucleotides or polynucleotides are transferred into cells for gene therapy.  
     
     
         29 . The use according to  claim 19  wherein the oligonucleotides or polynucleotides are transferred into cells for genetic immunisation (for the generation of antibodies) in whole organisms.  
     
     
         30 . The use according to any one of  claims 19  to  26  wherein the oligonucleotides or polynucleotides are transferred into cells in culture.  
     
     
         31 . The use of a spermine:peptide-based surfactant compound of any one of  claims 1  to  18  to facilitate the transfer of a polynucleotide or an anti-infective compounds into prokaryotic or eukaryotic organism for use in anti-infective therapy.  
     
     
         32 . The use of a spermine:peptide-based surfactant compound of any one of  claims 1  to  18  to facilitate the adhesion of cells in culture to each other or to a solid or semi-solid surface.  
     
     
         33 . A process for preparing spermine:peptide-based surfactant compounds of  claim 1  which process comprises adding amino acids or peptides to a hydrocarbylated spermine backbone.