Chapter

Heparin - A Century of Progress

Volume 207 of the series Handbook of Experimental Pharmacology pp 159-176

Date:

Heparin and Heparan Sulfate: Analyzing Structure and Microheterogeneity

  • Zachary ShriverAffiliated withKoch Institute for Integrative Cancer Research, Massachusetts Institute of TechnologyDepartment of Biological Engineering, Massachusetts Institute of Technology
  • , Ishan CapilaAffiliated withMomenta Pharmaceuticals Inc.
  • , Ganesh VenkataramanAffiliated withMomenta Pharmaceuticals Inc.
  • , Ram SasisekharanAffiliated withKoch Institute for Integrative Cancer Research, Massachusetts Institute of TechnologyDepartment of Biological Engineering, Massachusetts Institute of Technology Email author 

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Abstract

The structural microheterogeneity of heparin and heparan sulfate is one of the major reasons for the multifunctionality exhibited by this class of molecules. In a physiological context, these molecules primarily exert their effects extracellularly by mediating key processes of cellular cross-talk and signaling leading to the modulation of a number of different biological activities including development, cell proliferation, and inflammation. This structural diversity is biosynthetically imprinted in a nontemplate-driven manner and may also be dynamically remodeled as cellular function changes. Understanding the structural information encoded in these molecules forms the basis for attempting to understand the complex biology they mediate. This chapter provides an overview of the origin of the structural microheterogeneity observed in heparin and heparan sulfate, and the orthogonal analytical methodologies that are required to help decipher this information.

Keywords

Heparan sulfate Heparin Microheterogeneity Biosynthesis Structural analysis Conformation Mass spectrometry Nuclear magnetic resonance Structure–function relationships.