US2006240562A1PendingUtilityA1

Cleavable surfactants and methods of use thereof

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Assignee: CAPRIOLI RICHARD MPriority: May 29, 2001Filed: Jul 6, 2006Published: Oct 26, 2006
Est. expiryMay 29, 2021(expired)· nominal 20-yr term from priority
C07F 9/10C07C 327/22C07C 255/41C07F 7/081C07C 65/03C07C 69/732Y10T436/25375Y10T436/107497Y10T436/10C07D 213/20C07F 9/092
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Claims

Abstract

Cleavable compositions and methods of use especially in MALDI MS analysis of hydrophobic proteins.

Claims

exact text as granted — not AI-modified
1 - 35 . (canceled)  
   
   
       36 . A compound, comprising: a cleavable surfactant including a MALDI matrix composition and a hydrophobic group joined together by a cleavable linker.  
   
   
       37 . The compound of  36 , wherein the cleavable linker is a disulfide linker, a thioester linker, or a ketal linker.  
   
   
       38 . The compound of  claim 36 , comprising: a cleavable surfactant including a cinnamic group and a hydrophobic group joined together by a cleavable linker.  
   
   
       39 . The compound of  claim 36 , comprising: a sinapinic group and a hydrophobic group joined together by a cleavable linker.  
   
   
       40 . A compound of the following Formula:  
     
       
         
         
             
             
         
       
       or a salt thereof, wherein:  
       Y is a group —H, —OH, or —(CH2) n  OH independently on each of C4, C5, or C6 and  
       wherein n is an integer of from 1 to 5 and wherein Y is H or C3;  
       X is a group OH or NH2; and  
       R is a group (CH 2 )mCH 3 , wherein m is an integer of from 1 to 19.  
     
   
   
       41 . The compound of  claim 40 , wherein X is OH.  
   
   
       42 . The compound of  claim 40 , wherein R is a group —(CH 2 ) 3 CH 3 , —(CH 2 ) 4 CH 3 , —(CH 2 ) 5 CH 3 , —(CH 2 ) 6 CH 3 , or —(CH 2 ) 7 CH 3 .  
   
   
       43 . A compound of the following formula:  
     
       
         
         
             
             
         
       
       or a salt thereof, wherein:  
       Y is a group —N(CH 3 ) 2 (CH 2 ) 3 SO 3   − , —N + (CH 3 ) 3 , —SO 3   − , or —SO 4   − , independently on each of C4, C5, or C6 and wherein Y is —H on C3;  
       X is a group OH or NH2; and  
       R is a group (CH 2 )mCH 3 , wherein m is an integer of from 1 to 19.  
     
   
   
       44 . The compound of  claim 43 , wherein X is OH.  
   
   
       45 . The compound of  claim 43 , wherein R is a group —(CH 2 ) 3 CH 3 , —(CH 2 ) 4 CH 3 , —(CH 2 ) 5 CH 3 , —(CH 2 ) 6 CH 3 , or —(CH 2 ) 7 CH 3 .  
   
   
       46 . A compound of the following formula:  
     
       
         
         
             
             
         
       
       or a salt thereof, wherein:  
       Y is a group —H, —OH, —(CH2) n  OH, —N(CH 3 ) 2 (CH 2 ) 3 SO 3   − , —N + (CH 3 ) 3 , —SO 3   − , or —SO 4   − , independently on each of C4, C5, or C6 and wherein n is an integer of from 1 to 5 and wherein Y is H on C3; and  
       X is a group —OH or —NH2.  
     
   
   
       47 . A compound of the formula:  
     
       
         
         
             
             
         
       
     
     or a salt thereof.  
   
   
       48 . A method for isolating a hydrophobic molecule, comprising: 
 providing a plasma comprising a hydrophobic molecule;    applying a cleavable surfactant with a polar head group and a hydrophobic tail to the plasma so that the surfactant engages the hydrophobic molecule;    cleaving the surfactant from the hydrophobic molecule, and    analyzing said hydrophobic molecule.    
   
   
       49 . The method of  claim 48 , further comprising the step of: 
 analyzing said hydrophobic molecule.    
   
   
       50 . The method of  claim 49 , wherein said analyzing step comprises MALDI MS.  
   
   
       51 . The method of  claim 48 , wherein said hydrophobic molecule is a polymer, peptide, polypeptide, proteins, components of a cell sample, component of a tissue sample, lipid, or extracellular component.  
   
   
       52 . The method of  claim 48 , further comprising an enzymatic digestion step of the hydrophobic molecule, said enzymatic digestion step occurring either before or after said cleaving step.  
   
   
       53 . The method of  claim 49 , wherein the polar head group is a MALDI MS matrix or precursor thereof.  
   
   
       54 . The method of  claim 49 , wherein the polar head group comprises a cinnamic acid, derivatives of cinnamic acid, sinapinic acid, alpha-cyano-4-hydroxycinnamic acid (αCHCA), or 2,5-dihydroxybenzoic acid (2,5-DHB).  
   
   
       55 . The method of  claim 48 , wherein the cleavable surfactant/detergent compound of the following formula:  
     
       
         
         
             
             
         
       
     
   
   
       56 . The method of  claim 55 , wherein the hydrophobic tail comprises an alkyl, alkenyl, or alkynyl group containing 2-20 carbons.  
   
   
       57 . The method of  claim 55 , wherein the cleavable linker is acid cleavable, fluoride cleavable, photocleavable, or a disulfide/thioester,  
   
   
       58 . The method of  claim 57 , wherein the cleavable linker is selected from the following:  
     
       
         
         
             
             
         
       
       where R 1  is independently —H or —(CH 2 ) 0-19 CH 3 ;  
       
         
           
           
               
               
           
         
       
       where R 1  is independently —CH 3 ,  
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       X is a group NH 2  or OH. R 1  is —H, —CH 3 , —F, —Cl, —Br, —I, or, —CN. Head groups are attached independently on each of C4, C5, and C6.  
     
   
   
       59 . The method of  claim 55 , wherein the polar head is cationic, anionic, Zwitterionic, a non-ionic carbohydrate, or a MALDI matrix.  
   
   
       60 . The method of  claim 59 , wherein the polar head group is selected from N + [(CH) 0-3 CH 3 ] 3 , P + [(CH) 0-3 CH 3 ] 3 ,  
     
       
         
         
             
             
         
       
     
     wherein n is 1-12; cystine; cystine containing peptides with 6 amino acids or less; furanose; pyranose; polysaccharides with 3 carbohydrates or less; polyethylene glycol; sinapinic acid MALDI matrices; α-cyano-4-hydroxycinnamic acid MALDI matrices; 2,5-dihydroxybenzoic acid; MALDI matrices; and 3,5-dihydroxybenzoic acid MALDI matrices.  
   
   
       61 . A cleavable surfactant/detergent compound of the following formula:  
     
       
         
         
             
             
         
       
     
   
   
       62 . The compound of  claim 61 , wherein the MALDI matrix is a sinapinic acid MALDI matrix, α-cyano-4-hydroxycinnamic acid MALDI matrix, 2,5-dihydroxybenzoic acid; MALDI matrix, or a 3,5-dihydroxybenzoic acid MALDI matrices.  
   
   
       63 . A method of isolating a hydrophobic sample comprising contacting said sample with a compound of  claim 62 .  
   
   
       64 . A method of performing electrophoresis on a sample, comprising 
 contacting said sample with a surfactant that is subsequently cleavable from sample, said surfactant being selected from                          wherein said cleavable linker is acid cleavable, fluoride cleavable, photocleavable, or a disulfide/thioester,    
   
   
       65 . A cleavable surfactant/detergent compound of the following formula:  
     
       
         
         
             
             
         
       
     
   
   
       66 . The compound of  claim 65 , wherein the hydrophobic tail comprises an alkyl, alkenyl, or alkynyl group containing 2-20 carbons.  
   
   
       67 . The compound of  claim 65 , wherein the cleavable linker is acid cleavable, fluoride cleavable, photocleavable, or a disulfide/thioester,  
   
   
       68 . The compound of  claim 67 , wherein the cleavable linker is selected from the following:  
     
       
         
         
             
             
         
       
     
     where R 1  is independently —H or —(CH 2 ) 0-19 CH 3 ,  
     
       
         
         
             
             
         
       
       R 1  is independently —CH 3 ,  
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       X is a group NH 2  or OH. R 1  is —H, —CH 3 , —F, —Cl, —Br, —I, or, —CN. Head groups are attached independently on each of C4, C5, and C6.  
     
   
   
       69 . The compound of  claim 65 , wherein the polar head is cationic, anionic, Zwitterionic, a non-ionic carbohydrate, or a MALDI matrix.  
   
   
       70 . The compound of  claim 69 , wherein the polar head group is selected from 
 N + [(CH) 0-3 CH 3 ] 3 , P + [(CH) 0-3 CH 3 ] 3 ,                          wherein n is 1-12; cystine; cystine containing peptides with 6 amino acids or less; furanose; pyranose; polysaccharides with 3 carbohydrates or less; polyethylene glycol; sinapinic acid MALDI matrices; α-cyano-4-hydroxycinnamic acid MALDI matrices; 2,5-dihydroxybenzoic acid; MALDI matrices; and 3,5-dihydroxybenzoic acid MALDI matrices.    
   
   
       71 . A compound of  claim 65 , of the following formula:  
     
       
         
         
             
             
         
       
     
   
   
       72 . A compound of  claim 65 , of the following formula:

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