Disulfide bond containing compounds and uses thereof

Abstract

There is provided a range of novel disulfide bond containing compounds. These disulfide bond containing compounds can be used in a variety of applications such as solid phase peptide synthesis, solid phase organic synthesis, formation of dendrimers, formation of macromolecules and formation cyclic peptides; and as a component of a delivery vehicle with a bioactive molecule.

1 . A compound of formula XI, or a salt thereof: 
       
         
           
           
               
               
           
         
       
       wherein R 8  is selected from the group consisting of hydrogen, a counterion, and a substituted or unsubstituted carboxylic acid protecting group; and
 R 9  and R 9 ′ are independently selected from the group consisting of hydrogen, substituted or unsubstituted C 1  to C 6  alkyl and a substituted or unsubstituted amine protecting group, or R 9  and R 9 ′ together form a substituted or unsubstituted amine protecting group. 
 
     
     
         2 . The compound according to  claim 1 , wherein R 8  is hydrogen, or R 8  is a carboxylic acid protecting group selected from C 1 -C 6  alkyl, benzyl including substituted benzyl including nitrobenzyl, 2,6-disubstituted phenyl, substituted silyl including trialkylsilyl, trihaloalkyl, trialkoxyalkyl and oxazolyl, each of which carboxylic acid protecting groups may be substituted or unsubstituted. 
     
     
         3 . The compound according to  claim 1  or  claim 2 , wherein each R 9  and R 9 ′ are independently selected from the group consisting of hydrogen, and an amino protecting group selected from the group consisting of alkoxycarbonyl, phenoxycarbonyl, benzyloxycarbonyl, acyl, phenyl, benzyl, allyl, vinyl, and sulfonyl, each of which groups may be substituted or unsubstituted, or R 9  and R 9 ′ together form methylidene, benzylidene or phthaloyl, each or which may be may be substituted or unsubstituted. 
     
     
         4 . The compound according to any one of  claim 1  to  claim 3 , wherein each R 9  and R 9 ′ is independently selected from the group consisting of hydrogen, fluorenylmethoxycarbonyl (Fmoc), t-butyloxycarbonyl (Boc), benzyloxycarbonyl (carboxybenzyl, Cbz), p-methoxybenzyloxycarbonyl (Moz, MeOZ), formyl, acetyl (Ac), trifluoroacetyl, trichloroacetyl, benzoyl (Bz), p-methoxyphenyl (PMP), benzyl (Bn), p-methoxybenzyl (PMB), 3,4-dimethoxybenzyl (DMPM), 2,4-dimethoxybenzyl (Dmb), triphenylmethyl (trityl, Tr), 4-methyltriphenylmethyl (4-methyltrityl, Mtt), 4-methoxytriphenylmethyl (4-methoxytrityl, Mmt), diphenylmethylene, N—1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl (Dde), benzene sulfonyl and p-toluenesulfonyl (tosyl), each of which groups may be substituted or unsubstituted. 
     
     
         5 . The compound according to any one of the preceding claims, wherein at least one of R 9  and R 9 ′ are hydrogen. 
     
     
         6 . The compound according to any one of the preceding claims, wherein at least one of OR 8 , R 9  and R 9 ′ are independently replaced by a bond to a complimentary amino acid, a peptide sequence, a bioactive molecule, a lipid, a tag, or a probe. 
     
     
         7 . A method of forming a peptide structure comprising the step of reacting the compound of any one of  claim 1  to  claim 6  with an amino acid or bioactive molecule. 
     
     
         8 . A peptide structure that comprises a compound of any one of  claim 1  to  claim 6 . 
     
     
         9 . A peptide structure produced using a compound of any one of  claim 1  to  claim 6 . 
     
     
         10 . The peptide structure of  claim 8  or  claim 9 , wherein the peptide structure is a linear peptide, cyclic peptide or dendrimeric structure. 
     
     
         11 . A delivery vehicle comprising a macromolecule that comprises a compound of any one of  claim 1  to  claim 6 , wherein the macromolecule is complexed with or bonded to a bioactive molecule. 
     
     
         12 . A delivery vehicle comprising a macromolecule that is produced using a compound of any one of  claim 1  to  claim 6 , wherein the macromolecule is complexed with or bonded to a bioactive molecule. 
     
     
         13 . The delivery vehicle of  claim 11  or  claim 12 , wherein the macromolecule further comprises a lipid. 
     
     
         14 . The delivery vehicle of  claim 13 , wherein the macromolecule forms liposomes, micelles, solid lipid particles, or any combination thereof. 
     
     
         15 . A method of delivering a bioactive molecule to a target site in a mammal including the step of providing the delivery vehicle of any one of  claims 11 - 14  to the mammal to thereby deliver the bioactive molecule. 
     
     
         16 . A tag or probe construct that comprises a compound of any one of  claim 1  to  claim 6  bonded to a tag or probe. 
     
     
         17 . A tag or probe construct produced using a compound of any one of  claim 1  to  claim 6  bonded to a tag or probe. 
     
     
         18 . A pharmaceutical composition for the treatment or prophylaxis of a disease, disorder or condition comprising an effective amount of the peptide structure of any one of  claim 8 - 10  or delivery vehicle of any one of  claim 11 - 14  and a pharmaceutically acceptable carrier, diluent and/or excipient. 
     
     
         19 . The peptide structure of  claim 10 , wherein the dendrimeric structure is 
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
         20 . The peptide structure of  claim 10 , wherein the dendrimeric structure is 
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
         21 . The peptide structure of  claim 10 , wherein the dendrimeric structure is 
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
         22 . The peptide structure of  claim 10 , wherein the dendrimeric structure is 
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
         23 . The compound according to any one of  claim 1  to  claim 6 , wherein the compound is lipidated.