A mechanistic analysis of the quantitation of α-hydroxy ketones by the bicinchoninic acid assay

Weiser, Jennifer; Ricapito, Nicole G.; Yueh, Alice; Weiser, E.L.; Putnam, David

doi:10.1016/j.ab.2012.08.009

Cited by 10 publications

(6 citation statements)

References 33 publications

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“…Because DHA and even-carbon diacids are components in the human metabolome, they have been previously explored as building blocks for implantable polymeric biomaterials [2,4,[8][9][10][11]24,25]. However, the synthesis of DHA-containing polymers can be problematic for two reasons.…”

Section: Discussionmentioning

confidence: 99%

“…To date, polycarbonates and polycarbonate-esters containing dihydroxyacetone (DHA) are reported in the literature [2][3][4][5][6][7]. The potential medical utility of DHA-based polymers include the prevention of postoperative seroma, the maintenance of hemostasis following organ ligation and the controlled release of medicines [8][9][10][11]. One challenge associated with the synthesis of DHA-based polymers is the intrinsic reactivity and instability of the C2 carbonyl group.…”

Section: Introductionmentioning

confidence: 99%

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One-step synthesis, biodegradation and biocompatibility of polyesters based on the metabolic synthon, dihydroxyacetone

et al. 2016

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The one-step synthesis of a polyester family containing dihydroxyacetone is described along with a quantitative analysis of in vitro/in vivo degradation kinetics and initial biocompatibility. Polyesters were synthesized by combining dihydroxyacetone, which is a diol found in the eukaryotic glucose metabolic pathway, with even-carbon aliphatic diacids (adipic, suberic, sebacic) represented in the long-chain alpha carboxylic acid metabolic pathway, by Schӧtten-Baumann acylation. We show that by using a crystalline monomeric form of dihydroxyacetone, well-defined polyesters can be formed in one step without protection and deprotection strategies. Both diacid length and polyester molecular weight were varied to influence polymer physical and thermal properties. Polyesters were generated with number-averaged (Mn) molecular weights ranging from 2200-11,500. Polydispersities were consistent with step-growth polymerization and ranged from 2 to 2.6. The melting (Tm) and recrystallization (Tc) temperatures were impacted in an unpredictable manner. Thermal transitions for the polyesters were highest for the adipic acid followed by suberic acid and sebacic acid, respectively. It was shown that the thermal response of the DHA-based polyesters was influenced by both the diacid length and molecular weight. In vitro degradation studies revealed first-order weight loss kinetics, the molecular weight loss followed first order kinetics with 25%-40% of the original mass remaining after 8 weeks. In vivo testing over 16 weeks highlighted that mass loss ranged from ∼70% to ∼6% depending upon initial molecular weight and diacid length. Histological analysis revealed rapid resolution of both acute and chronic inflammatory responses, normal foreign body responses were observed and no inflammation was present after week 4. This one-step synthesis proved robust with unique copolymers warranting further study as potential biomaterials.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

One-step synthesis, biodegradation and biocompatibility of polyesters based on the metabolic synthon, dihydroxyacetone

et al. 2016

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“…ab193969; Abcam, Cambridge, UK) to determine the IFN-γ protein expression level in the mice spleen, obtained during surgery following sacrifice. Briefly, the spleen was homogenized in 1 ml of PBS containing 1% Triton X-100 using the plunger of a 10-ml syringe, and centrifuged at 7155 x g for 5 min at 4˚C, and the total protein concentration of the supernatant was determined using a bicinchoninic acid assay as previously described (19). IFN-γ antibody (catalogue no.…”

Section: Enzyme-linked Immunosorbent Assay (Elisa)mentioning

confidence: 99%

Preclinical trial of the multi-targeted lenvatinib in combination with cellular immunotherapy for treatment of renal cell carcinoma

Cai

Tang

Shen

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Lenvatinib is an oral, multi-targeted tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor β, RET and KIT. Cellular immunotherapy has the potential to be a highly targeted treatment, with low toxicity to normal tissues and a high capacity to eradicate tumor tissue. The present study assessed the safety, maximum tolerated dose (MTD) and preliminary antitumor activity of lenvatinib and cellular immunotherapy in a murine model of renal cell carcinoma (RCC). The present study used a therapeutic dose of 0.12 mg lenvatinib and/or 10 4 rat uterine cancer adenocarcinoma (RuCa)-sensitized lymphocytes administered once daily continuously in 7-day cycles. Tumor regression was observed in mice with RCC following treatment with lenvatinib and 10 4 RuCa-sensitized lymphocytes. MTD was established as once daily administration of 0.18 mg lenvatinib and 10 6 RuCa-sensitized lymphocytes. The most common treatment-related adverse effects observed were fatigue (40%), mucosal inflammation (30%), proteinuria, diarrhea, vomiting, hypertension and nausea (all 40%). Combination therapy using lenvatinib and cellular immunotherapy enhanced the antitumor effect induced by single treatments and prolonged the survival of mice with RCC compared with either of the single treatments. Treatment with lenvatinib (0.12 mg) combined with 10 4

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“…In addition to tablet erosion studies visualized by scanning electron microscopy, degradation of the polymer backbone can be tracked utilizing the bicinchoninic acid assay, which Putnam et al discovered to be a valuable tool in quantitatively measuring α -hydroxy ketones, such as DHA, in solution. 187 Zhuo et al report that upon deprotection of the pDHA homopolymer, hydrolytic degradation of the associated carbonate bonds drastically increases. 117 The results suggest that percent deprotection of pDHA in DHA-based materials is a potential control parameter in drug release technologies.…”

Section: Dihydroxyacetone Synthonsmentioning

confidence: 99%

Synthetic Biomaterials from Metabolically Derived Synthons

et al. 2016

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The utility of metabolic synthons as the building blocks for new biomaterials is based on the early application and success of hydroxy acid based polyesters as degradable sutures and controlled drug delivery matrices. The sheer number of potential monomers derived from the metabolome (e.g., lactic acid, dihydroxyacetone, glycerol, fumarate) gives rise to almost limitless biomaterial structural possibilities, functionality, and performance characteristics, as well as opportunities for the synthesis of new polymers. This review describes recent advances in new chemistries, as well as the inventive use of traditional chemistries, toward the design and synthesis of new polymers. Specific polymeric biomaterials can be prepared for use in varied medical applications (e.g., drug delivery, tissue engineering, wound repair, etc.) through judicious selection of the monomer and backbone linkage.

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A mechanistic analysis of the quantitation of α-hydroxy ketones by the bicinchoninic acid assay

Cited by 10 publications

References 33 publications

One-step synthesis, biodegradation and biocompatibility of polyesters based on the metabolic synthon, dihydroxyacetone

One-step synthesis, biodegradation and biocompatibility of polyesters based on the metabolic synthon, dihydroxyacetone

Preclinical trial of the multi-targeted lenvatinib in combination with cellular immunotherapy for treatment of renal cell carcinoma

Synthetic Biomaterials from Metabolically Derived Synthons

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