The Experts below are selected from a list of 108 Experts worldwide ranked by ideXlab platform

Charlotte C Williams - One of the best experts on this subject based on the ideXlab platform.

  • Cancer-targeting antibody-drug conjugates: Site-specific conjugation of doxorubicin to anti-EGFR 528 Fab′ through a polyethylene glycol linker
    Australian Journal of Chemistry, 2011
    Co-Authors: Lisa P T Hong, Larissa Doughty, Gregory Coia, Judith A Scoble, Charlotte C Williams
    Abstract:

    Antibody–drug conjugates have been prepared to examine the effect that attaching small-molecule drugs to an antibody fragment has on antibody activity. The anticancer drug doxorubicin was covalently attached through a polyethylene glycol linker to a cancer-targeting, anti-epidermal growth factor receptor antibody fragment (Fab′). The reactivity of Maleimide was compared with a substituted Maleimide Derivative (citraconimide) in conjugation reactions with cysteine residues on a Fab′. Introduction of polyethylene glycol increased aqueous solubility of the cytotoxic drug, which led to an improvement in overall yield of the conjugation reaction with the antibody fragment. Antibody–drug conjugates prepared retained activity of the parent antibody, as determined by antigen binding experiments measured by surface plasmon resonance.

  • Cancer-targeting Antibody–Drug Conjugates: Site-specific Conjugation of Doxorubicin to Anti-EGFR 528 Fab' through a Polyethylene Glycol Linker
    Australian Journal of Chemistry, 2011
    Co-Authors: Lisa P T Hong, Larissa Doughty, Gregory Coia, Judith A Scoble, Charlotte C Williams
    Abstract:

    Antibody–drug conjugates have been prepared to examine the effect that attaching small-molecule drugs to an antibody fragment has on antibody activity. The anticancer drug doxorubicin was covalently attached through a polyethylene glycol linker to a cancer-targeting, anti-epidermal growth factor receptor antibody fragment (Fab′). The reactivity of Maleimide was compared with a substituted Maleimide Derivative (citraconimide) in conjugation reactions with cysteine residues on a Fab′. Introduction of polyethylene glycol increased aqueous solubility of the cytotoxic drug, which led to an improvement in overall yield of the conjugation reaction with the antibody fragment. Antibody–drug conjugates prepared retained activity of the parent antibody, as determined by antigen binding experiments measured by surface plasmon resonance.

Martin W. Brechbiel - One of the best experts on this subject based on the ideXlab platform.

Marcel Tabak - One of the best experts on this subject based on the ideXlab platform.

  • stratum corneum protein dynamics as evaluated by a spin label Maleimide Derivative effect of urea
    Biophysical Journal, 2001
    Co-Authors: Antonio Alonso, Wilmar Pereira Dos Santos, Sergio Jacintho Leonor, J G Santos, Marcel Tabak
    Abstract:

    The stratum corneum (SC) protein dynamics in the sulfhydryl group regions was studied by electron paramag- netic resonance (EPR) spectroscopy of a covalently attached Maleimide Derivative spin label. A two-state model for the nitroxide described the coexistence of two spectral components in the EPR spectra. The so-called strongly immobilized component arises from a spin-label fraction with the nitroxide moiety hydrogen-bonded to protein (rigid structure) and the weakly immobilized component is provided by the spin labels with higher mobility (10 times greater) exposed to the aqueous environment. The relative populations between these two states are in thermodynamic equilibrium. The apparent energetic gain for the nitroxide to form a hydrogen bond with the backbone rather than to be dissolved in the local environment was 10 kcal/mol in the temperature range of 2-30°C and 6 kcal/mol in the range of 30 -70°C. Urea treatment caused a drastic increase in the segmental motion of the polypeptide chains that was completely reversible by its removal. Our analyses also indicated that the urea induced unfolding of the SC proteins opening the thiol group cavities. This work can also be useful to improve the spectral analysis of site-directed spin-labeling, especially for a more quantitative description of the nitroxide side chain mobility.

  • stratum corneum protein mobility as evaluated by a spin label Maleimide Derivative
    Biochimica et Biophysica Acta, 2000
    Co-Authors: Antonio Alonso, J G Santos, Marcel Tabak
    Abstract:

    Abstract The molecular dynamics in the vicinity of sulfhydryl groups of stratum corneum (SC) proteins has been studied by electron paramagnetic resonance (EPR) spectroscopy of Maleimide spin labels covalently bound to the proteins. The total amount of bound Maleimide was around 4 nmol per mg of SC. We have interpreted the coexistence of two spectral components in the EPR spectra by a two-state model with a fraction of label hydrogen bonded to proteins and another fraction exposed to the aqueous environment. We showed that the relative populations among these two states, determined by spectral simulation, are in thermodynamic equilibrium. The calculated energetic gain for the nitroxide to form hydrogen bond with SC proteins rather than to be dissolved in the buffer was ∼12 kcal/mol in the temperature range of 2–30°C and ∼5 kcal/mol in the range of 30–86°C. Temperature profiles of other EPR parameters related to the rotational diffusion of the probe also showed changes in the temperature interval of 26–42°C, suggesting alterations in the vibration modes of SC proteins which are sensitive to higher motional freedom above 26–42°C. We also compared samples of intact and lipid-depleted SC and we found that the delipidization process does not alter significantly the backbone mobility in the SH group regions, but the data suggest that the protein cavity is more open in the case of the delipidized samples. These results contribute to the understanding of the protein participation in the barrier function of SC, and can be useful to improve the spectral analysis of site-directed spin labeling, particularly for a more quantitative description of the dynamic modes of the nitroxide side chains.

Lisa P T Hong - One of the best experts on this subject based on the ideXlab platform.

  • Cancer-targeting antibody-drug conjugates: Site-specific conjugation of doxorubicin to anti-EGFR 528 Fab′ through a polyethylene glycol linker
    Australian Journal of Chemistry, 2011
    Co-Authors: Lisa P T Hong, Larissa Doughty, Gregory Coia, Judith A Scoble, Charlotte C Williams
    Abstract:

    Antibody–drug conjugates have been prepared to examine the effect that attaching small-molecule drugs to an antibody fragment has on antibody activity. The anticancer drug doxorubicin was covalently attached through a polyethylene glycol linker to a cancer-targeting, anti-epidermal growth factor receptor antibody fragment (Fab′). The reactivity of Maleimide was compared with a substituted Maleimide Derivative (citraconimide) in conjugation reactions with cysteine residues on a Fab′. Introduction of polyethylene glycol increased aqueous solubility of the cytotoxic drug, which led to an improvement in overall yield of the conjugation reaction with the antibody fragment. Antibody–drug conjugates prepared retained activity of the parent antibody, as determined by antigen binding experiments measured by surface plasmon resonance.

  • Cancer-targeting Antibody–Drug Conjugates: Site-specific Conjugation of Doxorubicin to Anti-EGFR 528 Fab' through a Polyethylene Glycol Linker
    Australian Journal of Chemistry, 2011
    Co-Authors: Lisa P T Hong, Larissa Doughty, Gregory Coia, Judith A Scoble, Charlotte C Williams
    Abstract:

    Antibody–drug conjugates have been prepared to examine the effect that attaching small-molecule drugs to an antibody fragment has on antibody activity. The anticancer drug doxorubicin was covalently attached through a polyethylene glycol linker to a cancer-targeting, anti-epidermal growth factor receptor antibody fragment (Fab′). The reactivity of Maleimide was compared with a substituted Maleimide Derivative (citraconimide) in conjugation reactions with cysteine residues on a Fab′. Introduction of polyethylene glycol increased aqueous solubility of the cytotoxic drug, which led to an improvement in overall yield of the conjugation reaction with the antibody fragment. Antibody–drug conjugates prepared retained activity of the parent antibody, as determined by antigen binding experiments measured by surface plasmon resonance.

Raya Mandler - One of the best experts on this subject based on the ideXlab platform.