Method for identifying or characterizing properties of polymeric units

Abstract

The invention relates to methods of identifying and characterizing properties of polymers to provide information about the polymer such as the charge of the polymer, the number and types or characteristics of units of the polymer and the sequence of the polymers. The invention also relates to methods of sequencing polymers such as nucleic acids, polypeptides and polysaccharides and methods for identifying a polysaccharide-protein interaction.

1 . A method of compositional analysis of chemical units of a HLGAG sample, comprising:
 a) providing a HLGAG sample,   b) applying an experimental constraint to the HLGAG sample to modify the HLGAG sample,   c) detecting a property of the HLGAG sample,   d) comparing the modified HLGAG sample to a reference database of a plurality of polysaccharides of identical molecular weight, charge, sulfation pattern or chain length as the sample HLGAG, wherein the polysaccharides of the reference database have also been subjected to the same experimental constraint as the sample HLGAG, and wherein the comparison provides compositional analysis of the HLGAG sample.   
   
   
       2 . The method of  claim 1 , wherein the experimental constraint applied to the HLGAG sample is one or more of enzymatic digestion, chemical digestion, chemical modification, interaction with a binding compound and chemical peeling. 
   
   
       3 . The method of  claim 1 , wherein the experimental constraint is complete degradation of the HLGAG sample into individual chemical units. 
   
   
       4 . The method of  claim 1 , wherein the step of detection comprises capillary electrophoresis. 
   
   
       5 . The method of  claim 1 , wherein the step of detection comprises reverse phase high performance liquid chromatography (RP-HPLC). 
   
   
       6 . The method of  claim 1 , wherein the step of detection comprises mass spectroscopy. 
   
   
       7 . The method of  claim 6 , wherein the mass spectroscopy is matrix laser desorption ionization mass spectroscopy (MALDI-MS). 
   
   
       8 . The method of  claim 1 , wherein the HLGAG sample is a heparin sample. 
   
   
       9 . The method of  claim 1 , wherein the HLGAG sample is a low molecular weight heparin (LMWH) sample. 
   
   
       10 . The method of  claim 1 , wherein the modified HLGAG sample is compared to a reference database of polysaccharides of identical molecular weight as the HLGAG sample, wherein the polysaccharides of the reference database have also been subjected to the same experimental constraint as the HLGAG sample. 
   
   
       11 . The method of  claim 10 , wherein the property of the HLGAG sample is the sulfation pattern. 
   
   
       12 . The method of  claim 1 , wherein the modified HLGAG sample is compared to a reference database of polysaccharides of identical chain length as the HLGAG sample, wherein the polysaccharides of the reference database have also been subjected to the same experimental constraint as the HLGAG sample. 
   
   
       13 . The method of  claim 12 , wherein the property of the HLGAG sample is the sulfation pattern. 
   
   
       14 . The method of  claim 1 , wherein the modified HLGAG sample is compared to a reference database of polysaccharides of identical sulfation pattern as the HLGAG sample, wherein the polysaccharides of the reference database have also been subjected to the same experimental constraint as the HLGAG sample. 
   
   
       15 . The method of  claim 14 , wherein the property is the type of basic building block of the HLGAG sample. 
   
   
       16 . The method of  claim 1 , further comprising e) eliminating from the reference database of polysaccharides, polysaccharides having properties that do not correspond to the property of the modified HLGAG sample. 
   
   
       17 . The method of  claim 16 , further comprising repeating steps c), d) and e) until the number of polysaccharides in the reference database falls below a predetermined threshold. 
   
   
       18 . A method of compositional analysis of chemical units of a heparin sample, comprising:
 a) providing a heparin sample,   b) applying an experimental constraint to the heparin sample to modify the heparin sample,   c) detecting a property of the heparin sample,   d) comparing the modified heparin sample to a reference database of a plurality of polysaccharides of identical molecular weight, charge, sulfation pattern or chain length as the heparin sample, wherein the polysaccharides of the reference database have also been subjected to the same experimental constraint as the heparin sample, and wherein the comparison provides compositional analysis of the heparin sample.   
   
   
       19 . The method of  claim 18 , wherein the experimental constraint applied to the heparin sample is one or more of enzymatic digestion, chemical digestion, chemical modification, interaction with a binding compound and chemical peeling. 
   
   
       20 . The method of  claim 18 , wherein the experimental constraint is complete degradation of the heparin sample into individual chemical units. 
   
   
       21 . The method of  claim 18 , wherein the step of detection comprises capillary electrophoresis. 
   
   
       22 . The method of  claim 18 , wherein the step of detection comprises reverse phase high performance liquid chromatography (RP-HPLC). 
   
   
       23 . The method of  claim 18 , wherein the step of detection comprises mass spectroscopy. 
   
   
       24 . The method of  claim 23 , wherein the mass spectroscopy is matrix laser desorption ionization mass spectroscopy (MALDI-MS). 
   
   
       25 . The method of  claim 18 , wherein the modified heparin sample is compared to a reference database of polysaccharides of identical molecular weight as the heparin sample, wherein the polysaccharides of the reference database have also been subjected to the same experimental constraint as the heparin sample. 
   
   
       26 . The method of  claim 25 , wherein the property of the heparin sample is the sulfation pattern. 
   
   
       27 . The method of  claim 18 , wherein the modified heparin sample is compared to a reference database of polysaccharides of identical chain length as the heparin sample, wherein the polysaccharides of the reference database have also been subjected to the same experimental constraint as the heparin sample. 
   
   
       28 . The method of  claim 27 , wherein the property of the heparin sample is the sulfation pattern. 
   
   
       29 . The method of  claim 18 , wherein the modified heparin sample is compared to a reference database of polysaccharides of identical sulfation pattern as the heparin sample, wherein the polysaccharides of the reference database have also been subjected to the same experimental constraint as the heparin sample. 
   
   
       30 . The method of  claim 29 , wherein the property is the type of basic building block of the heparin sample. 
   
   
       31 . The method of  claim 18 , further comprising e) eliminating from the reference database of polysaccharides, polysaccharides having properties that do not correspond to the property of the modified heparin sample. 
   
   
       32 . The method of  claim 31 , further comprising repeating steps c), d) and e) until the number of polysaccharides in the reference database falls below a predetermined threshold.