Confrormational studies on human transferrin

Hadden, Jonathan M.; Haris, Parvez I.; Srai, K; Chapman, D.

doi:10.1042/bst020200s

Cited by 3 publications

(3 citation statements)

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“…Thus, iron release was not expected at pH 6.4, justifying the fact of our results not showing differences in the CD spectra between pH 7.4 and 6.4. Additionally, the FTIR results showed that iron release did not significantly change the secondary structure of the protein ( p < 0.05), as already reported by other authors . Despite the results obtained suggesting conformation changes of the protein at pH 3.4, these are extremely acidic conditions that are not expected to occur under physiological conditions.…”

Section: Resultssupporting

confidence: 80%

“…Additionally, the FTIR results showed that iron release did not significantly change the secondary structure of the protein ( p < 0.05), as already reported by other authors. 45 Despite the results obtained suggesting conformation changes of the protein at pH 3.4, these are extremely acidic conditions that are not expected to occur under physiological conditions. Since at tumoral pH (6.4) no major conformational changes were observed, it is not expected that the Tf loses its biological activity.…”

Section: Resultsmentioning

confidence: 90%

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Transferrin-Conjugated PLGA Nanoparticles for Co-Delivery of Temozolomide and Bortezomib to Glioblastoma Cells

Ramalho

Torres

Loureiro

et al. 2023

ACS Appl. Nano Mater.

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Glioblastoma (GBM) represents almost half of primary brain tumors, and its standard treatment with the alkylating agent temozolomide (TMZ) is not curative. Treatment failure is partially related to intrinsic resistance mechanisms mediated by the O6methylguanine-DNA methyltransferase (MGMT) protein, frequently overexpressed in GBM patients. Clinical trials have shown that the anticancer agent bortezomib (BTZ) can increase TMZ's therapeutic efficacy in GBM patients by downregulating MGMT expression. However, the clinical application of this therapeutic strategy has been stalled due to the high toxicity of the combined therapy. The codelivery of TMZ and BTZ through nanoparticles (NPs) of poly(lacticco-glycolic acid) (PLGA) is proposed in this work, aiming to explore their synergistic effect while decreasing the drug's toxicity. The developed NPs were optimized by central composite design (CCD), then further conjugated with transferrin (Tf) to enhance their GBM targeting ability by targeting the blood−brain barrier (BBB) and the cancer cells. The obtained NPs exhibited suitable GBM cell delivery features (sizes lower than 200 nm, low polydispersity, and negative surface charge) and a controlled and sustained release for 20 days. The uptake and antiproliferative effect of the developed NPs were evaluated in in vitro human GBM models. The obtained results disclosed that the NPs are rapidly taken up by the GBM cells, promoting synergistic drug effects in inhibiting tumor cell survival and proliferation. This cytotoxicity was associated with significant cellular morphological changes. Additionally, the biocompatibility of unloaded NPs was evaluated in healthy brain cells, demonstrating the safety of the nanocarrier. These findings prove that co-delivery of BTZ and TMZ in Tf-conjugated PLGA NPs is a promising approach to treat GBM, overcoming the limitations of current therapeutic strategies, such as drug resistance and increased side effects.

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Section: Resultssupporting

confidence: 80%

Section: Resultsmentioning

confidence: 90%

Transferrin-Conjugated PLGA Nanoparticles for Co-Delivery of Temozolomide and Bortezomib to Glioblastoma Cells

Ramalho

Torres

Loureiro

et al. 2023

ACS Appl. Nano Mater.

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“…Figure 5 and Table 1 showed the quantitative assessments of ApoHST secondary structure. According to the literature [32,33], the amide I band of free ApoHST secondary structure consists of β-sheet (23%), β-turn (10%), αhelix (53%), and β-antiparallel (14%). The α-helix components were the largest which inferred the fact that ApoHST primarily occurred in the α-helix conformation.…”

Section: Resultsmentioning

confidence: 99%

Spectroscopic Studies for Rhodium (III) Binding to Apo-Transferrin

Bratty

Alhazmi

Najmi

et al. 2022

Journal of Chemistry

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Transferrin belongs to a class of monomeric glycoproteins, which sequestrate and transport iron inside the body. Apart from iron, transferrin binds with various other metal ions and is assumed to deliver medicinally important metal ions to cells. Hence, the investigation of binding characteristics may provide crucial information for new drug developments. To study the biological impacts of medicinally important metal ions, in this work, we explored the binding behavior of Rh(III) ion with serum apo-transferrin (ApoHST) using FT-IR and UV-Vis spectroscopy. In FT-IR, interaction of Rh(III) with ApoHST was studied at three concentrations (0.25, 0.5, and 1 mM) of metal ion at different time intervals (15, 30, and 60 min). The IR spectra of Rh(III)-ApoHST coordinates revealed a marked reduction in amide I and II band intensities with alterations in band positions. The α-helical part of protein secondary structure reduced considerably (from 53% to 49%, 42%, and 39%), followed by an increment in β-sheet and β-turn components with the increasing concentrations of metal ion. Saturation level reached at 1 mM concentration of Rh(III) ion. In the UV-Vis spectroscopic study, absorption of metal ion-protein coordinates successively raised as concentration of Rh(III) ion increased. The binding constant (K) was calculated as 1.16 × 10 4 M − 1 , which showed a strong binding of the test metal ion with the protein. Upon coordination with a metal ion, the microenvironment of aromatic protein residues changed, which was detected by these spectroscopic techniques. The results revealed the existence of a significant interaction between Rh (III) ion and ApoHST. These research outcome may present new insight into the possible utilization of Rh(III) ion-based compounds in biomedicine. However, more investigations are needed to interpret the exact cellular mechanism.

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