Structural peculiarity and antithrombin binding region profile of mucosal bovine and porcine heparins

Naggi, Annamaria; Gardini, Cristina; Pedrinola, Giacomo; Mauri, Lucio; Urso, Elena; Алексеева, Анна; Casu, Benito; Cassinelli, Giuseppe; Guerrini, Marco; Iacomini, Marcello; Baigorria, Valentina; Torri, Giangiacomo

doi:10.1016/j.jpba.2015.10.001

Cited by 34 publications

(47 citation statements)

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“…The bovine lung crude shows the highest degree of sulfation and lowest content of acetylation and nonsulfated uronic acid. The lower 6- O -sulfation of the bovine mucosa crude agree with those observed in the corresponding API [ 25 ], while the degree of sulfation and amount of N -acetylation measured for the ovine crude samples is intermediate to that of bovine lung and porcine mucosa heparin, as also observed by the integration of C13 spectra of the purified heparin samples [ 24 ]. The greater structural detail obtained applying the HSQC method allows the detection of minor residues in crude heparin, such as G2S, that is more abundant in BMHC compared to ovine or porcine heparins [ 25 ].…”

Section: Resultssupporting

confidence: 59%

“…As porcine, bovine, and ovine API heparins differ in many aspects of their structure and activity [ 21 , 22 , 23 , 24 , 25 ], it is important to verify if their structural differences can be observed in the corresponding crude. Six heparin crude samples from bovine intestinal mucosa (BMHC), two from bovine lung (BLHC) and three from ovine intestinal mucosa (OMHC) were characterized by proton and HSQC analysis.…”

Section: Resultsmentioning

confidence: 99%

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Combining NMR Spectroscopy and Chemometrics to Monitor Structural Features of Crude Hep-arin

et al. 2017

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Because of the complexity and global nature of the heparin supply chain, the control of heparin quality during manufacturing steps is essential to ensure the safety of the final active pharmaceutical ingredient (API). For this reason, there is a need to develop consistent analytical methods able to assess the quality of heparin early in production (i.e., as the crude heparin before it is purified to API under cGMP conditions). Although a number of analytical techniques have been applied to characterize heparin APIs, few of them have been applied for crude heparin structure and composition analyses. Here, to address this issue, NMR spectroscopy and chemometrics were applied to characterize 88 crude heparin samples. The samples were also analyzed by strong anion exchange HPLC (SAX-HPLC) as an orthogonal check of the purity levels of the crudes analyzed by NMR. The HPLC data showed that the chemometric analysis of the NMR data differentiated the samples based on their purity. These orthogonal approaches differentiated samples according their glycosaminoglycan (GAG) composition and their mono and disaccharide composition and structure for each GAG family (e.g., heparin/heparan, dermatan sulfate, and chondroitin sulfate A). Moreover, quantitative HSQC and multivariate analysis (PCA) were used to distinguish between crude heparin of different animal and tissue sources.

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Section: Resultssupporting

confidence: 59%

Section: Resultsmentioning

confidence: 99%

Combining NMR Spectroscopy and Chemometrics to Monitor Structural Features of Crude Hep-arin

et al. 2017

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“…Differences among heparins obtained from different animal sources were recently reported elsewhere 21 22 23 .The results obtained via NMR spectroscopy presented in these articles also suggest that heparins from porcine and bovine intestine have dissimilar structures. However, none of these works thoroughly correlate the molecular weight and disaccharide composition of those different heparins with their anticoagulant and antithrombotic potencies, as reported here.…”

Section: Discussionsupporting

confidence: 60%

Structural and haemostatic features of pharmaceutical heparins from different animal sources: challenges to define thresholds separating distinct drugs

Tovar

Santos

Capillé

et al. 2016

Sci Rep

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Heparins extracted from different animal sources have been conventionally considered effective anticoagulant and antithrombotic agents despite of their pharmacological dissimilarities. We performed herein a systematic analysis on the physicochemical properties, disaccharide composition, in vitro anticoagulant potency and in vivo antithrombotic and bleeding effects of several batches of pharmaceutical grade heparins obtained from porcine intestine, bovine intestine and bovine lung. Each of these three heparin types unambiguously presented differences in their chemical structures, physicochemical properties and/or haemostatic effects. We also prepared derivatives of these heparins with similar molecular weight differing exclusively in their disaccharide composition. The derivatives from porcine intestinal and bovine lung heparins were structurally more similar with each other and hence presented close anticoagulant activities whereas the derivative from bovine intestinal heparin had a higher proportion of 6-desulfated α-glucosamine units and about half anticoagulant activity. Our findings reasonably indicate that pharmaceutical preparations of heparin from different animal sources constitute distinct drugs, thus requiring specific regulatory rules and therapeutic evaluations.

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“…Heparin from bovine lung differs markedly in the degree of sulphation from porcine intestinal mucosal heparin (22), and both are different from bovine intestinal mucosal heparin (47). We can speculate that these differences in structure and in relative content of heparin vs, chondroitin/dermatan sulphate may have functional significance in the context of each particular tissue and species.…”

Section: Characterization Of Heparin Released From Mast Cellsmentioning

confidence: 92%

Biochemical and functional characterization of glycosaminoglycans released from degranulating rat peritoneal mast cells: Insights into the physiological role of endogenous heparin

Lever

Smailbegovic

Riffo‐Vasquez

et al. 2016

Pulmonary Pharmacology & Therapeutics

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Structural peculiarity and antithrombin binding region profile of mucosal bovine and porcine heparins

Cited by 34 publications

References 36 publications

Combining NMR Spectroscopy and Chemometrics to Monitor Structural Features of Crude Hep-arin

Combining NMR Spectroscopy and Chemometrics to Monitor Structural Features of Crude Hep-arin

Structural and haemostatic features of pharmaceutical heparins from different animal sources: challenges to define thresholds separating distinct drugs

Biochemical and functional characterization of glycosaminoglycans released from degranulating rat peritoneal mast cells: Insights into the physiological role of endogenous heparin

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