Efficient activation of carboxyl polysaccharides for the preparation of conjugates

Farkas, Pavol; Bystrický, Slavomı́r

doi:10.1016/j.carbpol.2006.07.013

Cited by 35 publications

(27 citation statements)

References 8 publications

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“…These may react with HA-thiols, resulting in disulfide bond formation, thereby affecting their structure and function. Furthermore, thiol-disulfide oxidoreduction of cell surface proteins plays a role in regulating critical cellular functions such as adhesion and proliferation 76 , and thus a blank hydrogel canvas without thiols allows more control over cellular behavior.…”

Section: Hyaluronic Acid Hydrogelsmentioning

confidence: 99%

“…With the goal of designing a simpler one-step, aqueousbased cross-linking system, we propose to synthesize HA hydrogels via Diels-Alder "click" chemistry. We have previously exploited this chemistry for conjugation of antibodies to nanoparticles for targeted drug delivery 76 , and others have used it to create synthetic polymeric hydrogels [56][57][58] . A furan-modified HA derivative can be synthesized and subsequently crosslinked via dimaleimide PEG, and the mechanical and degradation properties of this hydrogel system can be controlled by varying the furan to maleimide molar ratio.…”

Section: Thesis Objectivementioning

confidence: 99%

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Diels−Alder Click Cross-Linked Hyaluronic Acid Hydrogels for Tissue Engineering

2011

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Hyaluronic acid (HA) is a naturally occurring polymer that holds considerable promise for tissue engineering applications. Current cross-linking chemistries often require a coupling agent, catalyst, or photoinitiator, which may be cytotoxic, or involve a multistep synthesis of functionalized-HA, increasing the complexity of the system. With the goal of designing a simpler one-step , aqueous-based cross-linking system, we synthesized HA hydrogels via Diels-Alder "click" chemistry. Furan-modified HA derivates were synthesized and cross-linked via dimaleimide poly(ethylene glycol). By controlling the furan to maleimide molar ratio, both the mechanical and degradation properties of the resulting Diels-Alder cross-linked hydrogels can be tuned. Rheological and degradation studies demonstrate that the Diels-Alder click reaction is a suitable cross-linking method for HA. These HA cross-linked hydrogels were shown to be cytocompatible and may represent a promising material for soft tissue engineering.iii

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Section: Hyaluronic Acid Hydrogelsmentioning

confidence: 99%

Section: Thesis Objectivementioning

confidence: 99%

Diels−Alder Click Cross-Linked Hyaluronic Acid Hydrogels for Tissue Engineering

2011

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“…Highly reactive and water soluble 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and efficient and water-stable reagent 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM). In our previous work, we demonstrated the superiority of DMTMM above EDC on polysaccharide carrier molecule [3]. Although there are many protocols for EDC coupling, e.g.…”

Section: Introductionmentioning

confidence: 99%

Comparison of EDC and DMTMM efficiency in glycoconjugate preparation

Farkaš

Čížová

Bekešová

et al. 2013

International Journal of Biological Macromolecules

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“…We introduced DMT-MM as a more efficient activating reagent than EDC due to its higher stability in aqueous solution, especially when using phosphate buffer (45). Studies have shown that the use of DMT-MM in coupling PS with small bioactive molecules or with microspheres resulted in higher reaction yields than conventional methodologies (46,47). Likewise, as shown by the HIC chromatograms of the conjugates, the amount of PS6B conjugated to rPspA1 is higher in the method that uses DMT-MM-mediated conjugation (55.0% Ϯ 6.0%) than in the reductive amination (24.0% Ϯ 2.6%).…”

Section: Discussionmentioning

confidence: 99%

Conjugation of Polysaccharide 6B from Streptococcus pneumoniae with Pneumococcal Surface Protein A: PspA Conformation and Its Effect on the Immune Response

Perciani

Barazzone

Goulart

et al. 2013

Clin Vaccine Immunol

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bDespite the substantial beneficial effects of incorporating the 7-valent pneumococcal conjugate vaccine (PCV7) into immunization programs, serotype replacement has been observed after its widespread use. As there are many serotypes currently documented, the use of a conjugate vaccine relying on protective pneumococcal proteins as active carriers is a promising alternative to expand PCV coverage. In this study, capsular polysaccharide serotype 6B (PS6B) and recombinant pneumococcal surface protein A (rPspA), a well-known protective antigen from Streptococcus pneumoniae, were covalently attached by two conjugation methods. The conjugation methodology developed by our laboratory, employing 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) as an activating agent through carboxamide formation, was compared with reductive amination, a classical methodology. DMT-MM-mediated conjugation was shown to be more efficient in coupling PS6B to rPspA clade 1 (rPspA1): 55.0% of PS6B was in the conjugate fraction, whereas 24% was observed in the conjugate fraction with reductive amination. The influence of the conjugation process on the rPspA1 structure was assessed by circular dichroism. According to our results, both conjugation processes reduced the alpha-helical content of rPspA; reduction was more pronounced when the reaction between the polysaccharide capsule and rPspA1 was promoted between the carboxyl groups than the amine groups (46% and 13%, respectively). Regarding the immune response, both conjugates induced functional anti-rPspA1 and anti-PS6B antibodies. These results suggest that the secondary structure of PspA1, as well as its reactive groups (amine or carboxyl) involved in the linkage to PS6B, may not play an important role in eliciting a protective immune response to the antigens.

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Efficient activation of carboxyl polysaccharides for the preparation of conjugates

Cited by 35 publications

References 8 publications

Diels−Alder Click Cross-Linked Hyaluronic Acid Hydrogels for Tissue Engineering

Diels−Alder Click Cross-Linked Hyaluronic Acid Hydrogels for Tissue Engineering

Comparison of EDC and DMTMM efficiency in glycoconjugate preparation

Conjugation of Polysaccharide 6B from Streptococcus pneumoniae with Pneumococcal Surface Protein A: PspA Conformation and Its Effect on the Immune Response

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