Identification of a novel structure in heparin generated by sequential oxidative-reductive treatment
Research article published in Analytical chemistry (2012)
Abstract
Unfractionated heparin is isolated from animal organs, predominantly porcine intestinal mucosa, and goes through an extensive process of purification before it can be used for pharmaceutical purposes. While the structural microheterogeneity of heparin is predominantly biosynthetically imprinted in the Golgi, subsequent steps involved in the purification and manufacture of commercial heparin can lead to the introduction of additional modifications. Postheparin crisis of 2008, it has become increasingly important to identify what additional structural diversity is introduced as a function of the purification process and thus can be determined as being heparin-related, as opposed to being an adulterant or contaminant, e.g., oversulfated chondroitin sulfate. Our study focuses on the identification of a previously unreported structure in heparin that arises due to specific steps used in the manufacturing process. This structure was initially observed as a disaccharide peak in a complete enzymatic digest of heparin, but its presence was later identified in the NMR spectra of intact heparin as well. Structural elucidation experiments involved isolation of this structure and analysis based on multidimensional NMR and liquid chromatography coupled with mass spectrometry (LC-MS). Heparin was also subjected to specific chemical reactions to determine which steps in the manufacturing process are responsible for this novel structure. Our results allowed for the definitive assignment of the structure of this novel process-related modification and enabled an identification of the putative steps in the process that give rise to the structure.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Summary
Unfractionated heparin is isolated from animal organs, predominantly porcine intestinal mucosa, and goes through an extensive process of purification before it can be used for pharmaceutical purposes.
Why This Matters for Hirudotherapy
This research identifies a previously unreported structural modification in unfractionated heparin that arises from specific steps used in the manufacturing and purification process, post-2008 heparin crisis. Using multidimensional NMR and LC-MS, the authors definitively assigned the structure of this novel process-related modification and identified putative manufacturing steps responsible for it, helping distinguish genuine heparin-related diversity from adulterants such as oversulfated chondroitin sulfate. The abstract does not specify the exact chemical nature of the manufacturing steps beyond describing them as 'specific steps.' There is no mention of leeches, hirudotherapy, or leech-derived anticoagulants, so the study has no direct relevance to the ASH domain.
Citation
Identification of a novel structure in heparin generated by sequential oxidative-reductive treatment
Beccati D et al. · Analytical chemistry, 2012
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