A Practical Method for the Synthesis of a Cyclosporine−Fluorescein Conjugate

Grote, Jonathan; Fishpaugh, Jeffrey R.; Rege, Sushil

doi:10.1021/op0501592

Cited by 4 publications

(2 citation statements)

References 12 publications

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“…However, this group embedded in the CsA core turned out to be highly hindered and poorly reactive. For instance, the conversion of CsA into its corresponding chloroformate derivative using phosgene required a one-week reaction with a large excess of reagent [ 43 ]. Extensive research in the field led to the discovery that condensation with chloro- or bromoacetic anhydride constituted the most efficient way for the derivatization of CsA [ 44 , 45 , 46 ].…”

Section: Resultsmentioning

confidence: 99%

New Nanoparticle Formulation for Cyclosporin A: In Vitro Assessment

et al. 2021

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Cyclosporin A (CsA) is a molecule with well-known immunosuppressive properties. As it also acts on the opening of mitochondrial permeability transition pore (mPTP), CsA has been evaluated for ischemic heart diseases (IHD). However, its distribution throughout the body and its physicochemical characteristics strongly limit the use of CsA for intravenous administration. In this context, nanoparticles (NPs) have emerged as an opportunity to circumvent the above-mentioned limitations. We have developed in our laboratory an innovative nanoformulation based on the covalent bond between squalene (Sq) and cyclosporin A to avoid burst release phenomena and increase drug loading. After a thorough characterization of the bioconjugate, we proceeded with a nanoprecipitation in aqueous medium in order to obtain SqCsA NPs of well-defined size. The SqCsA NPs were further characterized using dynamic light scattering (DLS), cryogenic transmission electron microscopy (cryoTEM), and high-performance liquid chromatography (HPLC), and their cytotoxicity was evaluated. As the goal is to employ them for IHD, we evaluated the cardioprotective capacity on two cardiac cell lines. A strong cardioprotective effect was observed on cardiomyoblasts subjected to experimental hypoxia/reoxygenation. Further research is needed in order to understand the mechanisms of action of SqCsA NPs in cells. This new formulation of CsA could pave the way for possible medical application.

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Section: Resultsmentioning

confidence: 99%

New Nanoparticle Formulation for Cyclosporin A: In Vitro Assessment

et al. 2021

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“…The high quantum efficiencies, characteristic spectroscopic signatures and sensitivity to the microenvironment enabled implementation of fluorescein based probes for sensing intermolecular interactions in various laboratory and diagnostics applications. Subsequently, it prompted the use of anti‐fluorescein antibodies for the capture and detection of fluorescein labeled molecules . Typically, anti‐fluorescein antibodies have remarkable specificity to fluorescein and strongly quench its emission and therefore, may also present an interest as parts of molecular sensors and switches …”

Section: Introductionmentioning

confidence: 99%

Three‐dimensional structure, binding, and spectroscopic characteristics of the monoclonal antibody 43.1 directed to the carboxyphenyl moiety of fluorescein

et al. 2016

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Unlike other known anti-fluorescein antibodies, the monoclonal antibody 43.1 is directed toward the fluorescein's carboxyl phenyl moiety. It demonstrates a very high affinity (KD ∼ 70 pM) and a fast association rate (kon ∼ 2 × 10(7) M(-1 ) s(-1) ). The three-dimensional structure of the Fab 43.1-fluorescein complex was resolved at 2.4 Å resolution. The antibody binding site is exclusively assembled by the CDR loops. It is comprised of a 14 Å groove-shaped entrance leading to a 9 Å by 7 Å binding pocket. The highly polar binding pocket complementary encloses the fluorescein's carboxyphenyl moiety and tightly fixes it by multiple hydrogen bonds. The fluorescein's xanthene ring is embedded in the more hydrophobic groove and stacked between the side chains of Tyr37L and of Arg99H providing conditions for an excited state electron transfer process. In comparison to fluorescein, the absorption spectrum of the complex in the visible region is shifted to the "red" by 23 nm. The complex demonstrates a very weak fluorescence (Φc = 0.0018) with two short lifetime components: 0.03 ns (47%) and 0.8 ns (24%), which reflects a 99.8% fluorescein emission quenching effect upon complex formation. The antibody 43.1 binds fluorescein with remarkable affinity, fast association rate, and strongly quenches its emission. Therefore, it may present a practical interest in applications such as molecular sensors and switches.

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Semi-synthesis of cyclosporins

Peel¹,

Scribner²

2015

Biochimica et Biophysica Acta (BBA) - General Subjects

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A Practical Method for the Synthesis of a Cyclosporine−Fluorescein Conjugate

Cited by 4 publications

References 12 publications

New Nanoparticle Formulation for Cyclosporin A: In Vitro Assessment

New Nanoparticle Formulation for Cyclosporin A: In Vitro Assessment

Three‐dimensional structure, binding, and spectroscopic characteristics of the monoclonal antibody 43.1 directed to the carboxyphenyl moiety of fluorescein

Semi-synthesis of cyclosporins

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