Detection of oligosaccharides

Abstract

Provided herein are processes for detecting oligosaccharides in a biological sample. In specific instances, the biological sample is provided from an individual suffering from a disorder associated with abnormal glycosaminoglycan accumulation.

1 - 30 . (canceled) 
     
     
         31 . A method of determining in an individual the presence, identity, and/or severity of an MPS IIIA or MPS IIIB disorder, the method comprising:
 (a) generating a biomarker comprising one or more saturated non-reducing end oligosaccharides, wherein the biomarker is generated by treating a population of heparan sulfate oligosaccharides, in or isolated from a biological sample from the individual, with at least one digesting glycosaminoglycan lyase, wherein prior to lyase treatment, the biomarker is not present in abundance in samples from individuals with the MPS IIIA or MPS IIIB disorder relative to individuals without the MPS IIIA or MPS IIIB disorder; and   (b) using an analytical instrument to detect the presence of and/or measure the amount of the biomarker produced and displaying or recording the presence of or the measure of the biomarker produced;   wherein the presence of and/or measure of the amounts of the biomarker are utilized to determine the presence, identity, and/or severity of the MPS III disorder; and   wherein the biomarker is selected from a group consisting of   Formula III: [GlcNS-IdoA-GlcN(Ac)0-1](SO 3 R)0-3;   Formula IV: [GlcNS-GlcA-GlcN(Ac)0-1](SO 3 R)0-2;   Formula V: [GlcNAc-IdoA-GlcN(Ac)0-1](SO 3 R)0-3;   Formula VI: [GlcNAc-GlcA-GlcN(Ac)0-1](SO 3 R)0-2;   Formula VIII: [GlcN-GlcA-GlcN(Ac)0-1](SO 3 R)0-4;   Formula IX: [GlcNAc6S-IdoA-GlcN(Ac)0-1](SO 3 R)0-3;   Formula X: [GlcNAc6S-GlcA-GlcN(Ac)0-1](SO 3 R)0-2;   GlcN-IdoA-GlcNAc;   GlcN-IdoA2S-GlcNAc;   GlcN-IdoA-GlcNS;   GlcN-IdoA-GlcNAc6S;   GlcN-IdoA2-GlcNAc6S; and   GlcN-IdoA-GlcNS6S.   
     
     
         32 . The method of  claim 31 , wherein the biomarker is of Formula V: [GlcNAc-IdoA-GlcN(Ac) 0 -1](SO 3 R) 0-3 ; or Formula VI: [GlcNAc-GlcA-GlcN(Ac) 0-1 ](SO 3 R) 0-2 . 
     
     
         33 . The method of  claim 32 , wherein the biomarker of Formula V is selected from a group consisting of GlcNAc-IdoA-GlcNAc, GlcNAc-IdoA2S-GlcNAc, GlcNAc-IdoA-GlcNS, GlcNAc-IdoA2S-GlcNS, GlcNAc-IdoA-GlcNAc6S, GlcNAc-IdoA2S-GlcNAc6S, GlcNAc-IdoA-GlcNS6S, and GlcNAc-IdoA2S-GlcNS6S. 
     
     
         34 . The method of  claim 32 , wherein the biomarker of Formula VI is selected from a group consisting of GlcNAc-GlcA-GlcNAc, GlcNAc-GlcA-GlcNS, GlcNAc-GlcA-GlcNAc6S, and GlcNAc-GlcA-GlcNS6S. 
     
     
         35 . The method of  claim 31 , wherein the biomarker is of Formula III: [GlcNS-IdoA-GlcN(Ac) 0-1 ](SO 3 R) 0-3 . 
     
     
         36 . The method of  claim 35 , wherein the biomarker of Formula III is selected from a group consisting of GlcNS-IdoA-GlcNAc, GlcNS-IdoA2S-GlcNAc, GlcNS-IdoA-GlcNS, GlcNS-IdoA2S-GlcNS, GlcNS-IdoA-GlcNAc65, GlcNS-IdoA2S-GlcNAc65, GlcNS-IdoA-GlcNS6S, and GlcNS-IdoA2S-GlcNS6S. 
     
     
         37 . The method of  claim 31 , wherein the biomarker is of Formula IV: [GlcNS-GlcA-GlcN(Ac) 0-1 ](SO 3 R) 0-2 . 
     
     
         38 . The method of  claim 37 , wherein the biomarker of Formula IV is selected from a group consisting of GlcNS-GlcA-GlcNAc, GlcNS-GlcA-GlcNS, GlcNS-GlcA-GlcNAc6S, or GlcNS-GlcA-GlcNS6S. 
     
     
         39 . The method of  claim 31 , wherein the biomarker is selected from a group consisting of GlcN-IdoA-GlcNAc, GlcN-IdoA2S-GlcNAc, GlcN-IdoA-GlcNS, GlcN-IdoA-GlcNAc6S, GlcN-IdoA2S-GlcNAc6S, and GlcN-IdoA-GlcNS6S. 
     
     
         40 . The method of  claim 31 , wherein the biomarker is of Formula VIII: [GlcN-GlcA-GlcN(Ac) 0-1 ](SO 3 R) 0-4 . 
     
     
         41 . The method of  claim 40 , wherein the biomarker of Formula VIII is selected from a group consisting of GlcN-GlcA-GlcNAc, GlcN-GlcA-GlcNS, GlcN-GlcA-GlcNAc6S, and GlcN-GlcA-GlcNS6S. 
     
     
         42 . The method of  claim 31 , wherein the biomarker is of Formula IX: [GlcNAc6S-IdoA-GlcN(Ac) 0-1 ](SO 3 R) 0-3 . 
     
     
         43 . The method of  claim 32 , wherein the biomarker of Formula IX is selected from a group consisting of GlcNAc6s-IdoA-GlcNAc, GlcNAc6s-IdoA2S-GlcNAc, GlcNAc6s-IdoA-GlcNS, GlcNAc6s-IdoA2S-GlcNS, GlcNAc6s-IdoA-GlcNAc6S, GlcNAc6s-IdoA2S-GlcNAc6S, GlcNAc6s-IdoA-GlcNS6S, and GlcNAc6s-IdoA2S-GlcNS6S. 
     
     
         44 . The method of  claim 31 , wherein the biomarker is of Formula X: [GlcNAc6S-GlcA-GlcN(Ac) 0-1 ](SO 3 R) 0-2 . 
     
     
         45 . The method of  claim 44 , wherein the biomarker of Formula X is selected from a group consisting of GlcNAc6S-GlcA-GlcNAc, GlcNAc6S-GlcA-GlcNS, GlcNAc6S-GlcA-GlcNAc6S, and GlcNAc6S-GlcA-GlcNS6S. 
     
     
         46 . The method of  claim 31 , wherein the method further comprises purifying the biomarker generated in step (a) to yield an isolated population of biomarkers. 
     
     
         47 . The method of  claim 46 , wherein the biomarker is purified using chromatography or electrophoresis. 
     
     
         48 . The method of  claim 31 , wherein the method further comprises tagging the biomarkers with a detectable label. 
     
     
         49 . The method of  claim 48 , wherein the detectable label is a mass label, a radio label, a fluorescent label, a chromophore label, or affinity label. 
     
     
         50 . The method of claim  1 , wherein the method is used to determine whether the individual is a heterozygous carrier of the MPS IIIA or MPS IIIB disorder.