DDM (Knudsen and Hubbell 1978; Rosevear et al. 1980; VanAken et al. 1986), and CHAPS – a
zwitterionic derivative of cholate (Hjelmeland et al. 1983) (see Fig. 2.1) – among tens of others.
Developing less aggressive detergents
(# 2018 by Francis Haraux)
With MP biochemistry maturing, the realization came that there is no silver bullet and that a
detergent that is well tolerated by a given MP cannot be used with the next one, which encouraged
diversifying existing molecules and experimenting with new structures. The development of MP
crystallization and solution NMR brought its own demands. Crystallographers prefer their detergents
to be nonionic, so as to avoid electrostatic repulsion between detergent belts, and to form small belts, so
as to leave as much protein surface free as possible to facilitate the formation of crystalline contacts.
They tend to use detergents with either sugar-based, polyoxyethylene-based, or aminoxyde-based
polar heads, which are more favorable to crystallization. NMR spectroscopists also want to form as
small MP/detergent complexes as possible, but they rather prefer them to repulse each other, so as to
prevent aggregation, and, because they work at high concentrations of protein and detergent and
relatively high temperature (to accelerate tumbling), they have a fine line to walk between keeping the
protein monodisperse and denaturing it. They often resort to detergents with zwitterionic polar heads,
such as dodecylphosphocholine (DPC) or dihexanoylphosphatidylcholine (DHPC, diC 6 PC) (Fig. 2.1).
As these activities developed, so did the panel of available detergents.
Developing a new detergent, validating its use for MP biochemistry and biophysics, setting up its
industrial synthesis, and bringing it efficiently to the market are ripe with pitfalls. Many promising
molecules have remained in drawers because their synthesis or purification was too complex; their
phase diagram left insufficient leeway for varying the temperature, concentration, and/or buffer
conditions; and their biochemical validation was insufficient or their marketing inefficient. Gaining a
following on a cluttered market demands that the new molecule can boast of serious advantages. It also
depends somewhat on chance, such as the new molecules being instrumental in a particularly
successful and eye-catching project. Among recent, original proposals, one may perhaps, somewhat
arbitrarily, mention tripod amphiphiles (Yu et al. 2000; Chae et al. 2008, 2013; Ehsan et al. 2017);
facial amphiphiles (Zhang et al. 2007, 2011; Chae et al 2010; Lee et al. 2013) (see Fig. 2.15, di-β-Dmaltoside cholane); DDM analogs with a melibiose polar head, yielding smaller micelles (Hutchison
et al. 2017), or with hydrophobic tails that either carry a terminal cyclohexyl group (the Cymal series;
see Ostermeier et al. 1997) or are branched (Hong et al. 2011; Zhang et al. 2011) or are comprised of
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2 Extracting Membrane Proteins from Their Native Environment
zwitterionic derivative of cholate (Hjelmeland et al. 1983) (see Fig. 2.1) – among tens of others.
Developing less aggressive detergents
(# 2018 by Francis Haraux)
With MP biochemistry maturing, the realization came that there is no silver bullet and that a
detergent that is well tolerated by a given MP cannot be used with the next one, which encouraged
diversifying existing molecules and experimenting with new structures. The development of MP
crystallization and solution NMR brought its own demands. Crystallographers prefer their detergents
to be nonionic, so as to avoid electrostatic repulsion between detergent belts, and to form small belts, so
as to leave as much protein surface free as possible to facilitate the formation of crystalline contacts.
They tend to use detergents with either sugar-based, polyoxyethylene-based, or aminoxyde-based
polar heads, which are more favorable to crystallization. NMR spectroscopists also want to form as
small MP/detergent complexes as possible, but they rather prefer them to repulse each other, so as to
prevent aggregation, and, because they work at high concentrations of protein and detergent and
relatively high temperature (to accelerate tumbling), they have a fine line to walk between keeping the
protein monodisperse and denaturing it. They often resort to detergents with zwitterionic polar heads,
such as dodecylphosphocholine (DPC) or dihexanoylphosphatidylcholine (DHPC, diC 6 PC) (Fig. 2.1).
As these activities developed, so did the panel of available detergents.
Developing a new detergent, validating its use for MP biochemistry and biophysics, setting up its
industrial synthesis, and bringing it efficiently to the market are ripe with pitfalls. Many promising
molecules have remained in drawers because their synthesis or purification was too complex; their
phase diagram left insufficient leeway for varying the temperature, concentration, and/or buffer
conditions; and their biochemical validation was insufficient or their marketing inefficient. Gaining a
following on a cluttered market demands that the new molecule can boast of serious advantages. It also
depends somewhat on chance, such as the new molecules being instrumental in a particularly
successful and eye-catching project. Among recent, original proposals, one may perhaps, somewhat
arbitrarily, mention tripod amphiphiles (Yu et al. 2000; Chae et al. 2008, 2013; Ehsan et al. 2017);
facial amphiphiles (Zhang et al. 2007, 2011; Chae et al 2010; Lee et al. 2013) (see Fig. 2.15, di-β-Dmaltoside cholane); DDM analogs with a melibiose polar head, yielding smaller micelles (Hutchison
et al. 2017), or with hydrophobic tails that either carry a terminal cyclohexyl group (the Cymal series;
see Ostermeier et al. 1997) or are branched (Hong et al. 2011; Zhang et al. 2011) or are comprised of
82
2 Extracting Membrane Proteins from Their Native Environment