This perspective illustrates the principles and applications of molecular recognition directed binding of transition metal complexes to proteins. After a brief introduction into non-covalent interactions and the importance of complementarity, the focus of the first part is on biological systems that rely on non-covalent forces for metal complex binding, such as proteins involved in bacterial iron uptake and the oxygen-storage protein myoglobin. The second part of the perspective will illustrate how the replacement of native with non-native metal-centres can give rise to artificial metalloenzymes with novel catalytic properties. Subsequently, examples of spectroscopic probes that exploit the characteristic photophysical properties of metal-complexes for the non-covalent labelling, visualisation and investigation of proteins will be described. Finally, the use of kinetically inert metal complexes as scaffolds in drug design will be discussed and it will be highlighted how the binding of metal ions or organometallic fragments to existing drugs or drug candidates can improve their activity or even alter their mode of action.

Dedicated to Professor Bernt Krebs on the occasion of his 70th birthdayDue to their distinct emission spectra and long lifetimes, lanthanide-based luminescent probes are particularly suited to biological applications. [1][2][3] To emit strongly, lanthanide ions require an antenna chromophore to absorb the energy of the light and transfer it to the emitting level of the lanthanide. Here we describe the development of a new type of luminescent probe for the visualization of integral membrane proteins (IMPs), which uses the tryptophan and tyrosine residues in the aromatic collar of an IMP as antenna chromophores (Figure 1 a). The luminescence of the terbium center bound in the head group of our amphiphilic probe is sensitized to those probe molecules that are in close proximity to the aromatic collar at the hydrophobic boundary of an IMP. Since aromatic collars are structural features that are specific to IMPs, our approach offers the opportunity to visualize these proteins selectively. In addition, this noncovalent labeling is potentially reversible, flexible, and minimally invasive.In conventional probes, the chromophore is usually covalently attached to a ligand that chelates the lanthanide or is directly coordinated to the lanthanide ion. In the context of cyclodextrin [4,5] and peptide chemistry [6,7] it has been demonstrated that noncovalent interactions can also be used to achieve sensitization, provided that the interactions increase the effective concentration of the antenna in the vicinity of the lanthanide ion. Similarly, micelles can be used to bring the energy-transfer components into close proximity. Fendler et al. demonstrated that naphthalene, if solubilized in the hydrophobic interior of sodium dodecyl sulfate (SDS) micelles, sensitizes Tb 3+ cations that are attracted to the head groups of the anionic surfactant.[8] Metallosurfactants offer the additional advantage of incorporating the metal ion into their polar head group, thereby localizing it at a micellar interface. [9] Our aim was to position the terbium-containing head group of our amphiphilic probe close to the aromatic collar of a surfactant-solubilized IMP to facilitate intermolecular energy transfer at the hydrophilic/hydrophobic interface. As gateways to the cell, IMPs are important drug targets. In current research, however, IMPs present a bottleneck due to difficult purification and crystallization. The IMPs have a higher content of aromatic amino acids than soluble proteins, [10] and the side chains of the tryptophan and tyrosine residues tend to be localized at the membrane/water interface, where they form a "collar" at the boundary between the polar and the nonpolar regions of the bilayer.As detailed in the Supporting Information, Tb 3+ was bound in the head group of H 3 -DTPA-2C 16 . [11,12] The resulting lipid analogue, complex )(H 2 O)] (Figure 1 b), was characterized by high-resolution ESI mass spectrometry, infrared spectroscopy, and elemental analysis. Furthermore, fluorescence spectroscopy confirmed that the complex on its o...

No abstract

Dedicated to Professor Bernt Krebs on the occasion of his 70th birthday Due to their distinct emission spectra and long lifetimes, lanthanide-based luminescent probes are particularly suited to biological applications. [1][2][3] To emit strongly, lanthanide ions require an antenna chromophore to absorb the energy of the light and transfer it to the emitting level of the lanthanide. Here we describe the development of a new type of luminescent probe for the visualization of integral membrane proteins (IMPs), which uses the tryptophan and tyrosine residues in the aromatic collar of an IMP as antenna chromophores (Figure 1 a). The luminescence of the terbium center bound in the head group of our amphiphilic probe is sensitized to those probe molecules that are in close proximity to the aromatic collar at the hydrophobic boundary of an IMP. Since aromatic collars are structural features that are specific to IMPs, our approach offers the opportunity to visualize these proteins selectively. In addition, this noncovalent labeling is potentially reversible, flexible, and minimally invasive.In conventional probes, the chromophore is usually covalently attached to a ligand that chelates the lanthanide or is directly coordinated to the lanthanide ion. In the context of cyclodextrin [4,5] and peptide chemistry [6,7] it has been demonstrated that noncovalent interactions can also be used to achieve sensitization, provided that the interactions increase the effective concentration of the antenna in the vicinity of the lanthanide ion. Similarly, micelles can be used to bring the energy-transfer components into close proximity. Fendler et al. demonstrated that naphthalene, if solubilized in the hydrophobic interior of sodium dodecyl sulfate (SDS) micelles, sensitizes Tb 3+ cations that are attracted to the head groups of the anionic surfactant. [8] Metallosurfactants offer the additional advantage of incorporating the metal ion into their polar head group, thereby localizing it at a micellar interface. [9] Our aim was to position the terbium-containing head group of our amphiphilic probe close to the aromatic collar of a surfactant-solubilized IMP to facilitate intermolecular energy transfer at the hydrophilic/hydrophobic interface. As gateways to the cell, IMPs are important drug targets. In current research, however, IMPs present a bottleneck due to difficult purification and crystallization. The IMPs have a higher content of aromatic amino acids than soluble proteins, [10] and the side chains of the tryptophan and tyrosine residues tend to be localized at the membrane/water interface, where they form a "collar" at the boundary between the polar and the nonpolar regions of the bilayer.As detailed in the Supporting Information, Tb 3+ was bound in the head group of H 3 -DTPA-2C 16 . [11,12] The resulting lipid analogue, complex [Tb(DTPA-2C 16 )(H 2 O)] (Figure 1 b), was characterized by high-resolution ESI mass spectrometry, infrared spectroscopy, and elemental analysis. Furthermore, fluorescence spectroscopy confirmed that the ...

No abstract