Biomedical Applications
15
Summary
Biomedical applications of amphipols (APols) are still in their infancy. However, some
projects have been initiated that appear promising and ought to stimulate further
developments. First, it has been demonstrated that a membrane protein from a pathogenic bacterium responsible for a widely distributed sexually transmitted infection, the
major outer membrane protein (MOMP) from Chlamydia trachomatis, can be used as
immunogen in the formulation of vaccines after being trapped with A8-35. A8-35trapped MOMP is considerably stabilized as compared to its detergent-solubilized
form, extending the thermal resistance and shelf life of the vaccine and increasing the
protection it confers to mice as compared to detergent-based formulations. Versions of
A8-35 carrying covalently linked adjuvants for co-delivery have been developed and,
according to the first results, appear to stimulate the immune response better than free
adjuvants. Second, internalization of A8-35 and its payload have been observed in cell
cultures. Third, the absence of toxicity of A8-35 and its distribution and elimination
when injected in mice by various routes have been characterized using fluorescent
variants of A8-35. These data provide a basis for the use of APols for delivering drugs,
e.g. hydrophobic anticancer peptides mimicking the transmembrane anchor of growth
factor receptors. The rich chemistry of APols and the fact that several APol molecules
bind to a given membrane protein provide exceptional opportunities for associating a
drug or antigen with adjuvants and/or targeting moieties.
15.1 Introduction
In Chap. 13, we have evoked one particular biomedical application of amphipols (APols), namely
using tagged APols to immobilize putative drug targets onto solid supports for the purpose of in vitro
drug screening or diagnostics. There are also prospects of in vivo uses for human therapeutics. The
absence of apparent toxicity of A8-35 when injected in mice or applied to cell cultures was established
quite early (Popot et al. 2003), raising the possibility that APols could be used for delivering drugs or
immunogens. Exploration of this avenue has been quite slow and is only at its beginning, but the first
observations are promising.
# Springer International Publishing AG, part of Springer Nature 2018
J. -L. Popot, Membrane Proteins in Aqueous Solutions, Biological and Medical Physics,
Biomedical Engineering, https://doi.org/10.1007/978-3-319-73148-3_15
659
15
Summary
Biomedical applications of amphipols (APols) are still in their infancy. However, some
projects have been initiated that appear promising and ought to stimulate further
developments. First, it has been demonstrated that a membrane protein from a pathogenic bacterium responsible for a widely distributed sexually transmitted infection, the
major outer membrane protein (MOMP) from Chlamydia trachomatis, can be used as
immunogen in the formulation of vaccines after being trapped with A8-35. A8-35trapped MOMP is considerably stabilized as compared to its detergent-solubilized
form, extending the thermal resistance and shelf life of the vaccine and increasing the
protection it confers to mice as compared to detergent-based formulations. Versions of
A8-35 carrying covalently linked adjuvants for co-delivery have been developed and,
according to the first results, appear to stimulate the immune response better than free
adjuvants. Second, internalization of A8-35 and its payload have been observed in cell
cultures. Third, the absence of toxicity of A8-35 and its distribution and elimination
when injected in mice by various routes have been characterized using fluorescent
variants of A8-35. These data provide a basis for the use of APols for delivering drugs,
e.g. hydrophobic anticancer peptides mimicking the transmembrane anchor of growth
factor receptors. The rich chemistry of APols and the fact that several APol molecules
bind to a given membrane protein provide exceptional opportunities for associating a
drug or antigen with adjuvants and/or targeting moieties.
15.1 Introduction
In Chap. 13, we have evoked one particular biomedical application of amphipols (APols), namely
using tagged APols to immobilize putative drug targets onto solid supports for the purpose of in vitro
drug screening or diagnostics. There are also prospects of in vivo uses for human therapeutics. The
absence of apparent toxicity of A8-35 when injected in mice or applied to cell cultures was established
quite early (Popot et al. 2003), raising the possibility that APols could be used for delivering drugs or
immunogens. Exploration of this avenue has been quite slow and is only at its beginning, but the first
observations are promising.
# Springer International Publishing AG, part of Springer Nature 2018
J. -L. Popot, Membrane Proteins in Aqueous Solutions, Biological and Medical Physics,
Biomedical Engineering, https://doi.org/10.1007/978-3-319-73148-3_15
659