Selective protein-surface sensing using ruthenium(II) tris(bipyridine) complexes.
Selective protein-surface sensing using ruthenium(II) tris(bipyridine) complexes.
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DOI：
10.1002/chem.200902368
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发表时间：
2010-01-04
影响因子：
4.3
通讯作者：
Wilson, Andrew J.
中科院分区：
文献类型：
--
作者：
Muldoon, James;Ashcroft, Alison E.;Wilson, Andrew J.
Inhibition of protein–protein interactions (PPIs) with designed molecules represents a key challenge in modern bio-organic chemistry.[1–3] In contrast to competitive enzyme inhibition,[4] in which small molecules are optimised to masquerade as a substrate (or transition-state analogue) and fit a well defined concave pocket or cleft, competitive inhibition of PPIs requires a molecule that must make discontinuous, noncovalent contacts over a much larger (> 800 Å2), surface-lacking, defined shape. Whilst high-throughput screening has identified inhibitors of some PPIs,[5, 6]—these are generally regarded as ‘lowhanging fruit’[2]—there remains a need to develop our basic understanding of how to design molecules that possess the features needed for protein-surface recognition. Building on fundamental studies of short peptide recognition,[7–9] a number of approaches in which a scaffold is used to project groups capable of making multivalent hydrophobic,[10] ionpairing [11–29] and metal–ligand interactions [30–33] with proteins have been described. In the current manuscript we illustrate that functionalised RuII tris-bipyridine complexes can be used as selective and low nanomolar sensors for cytochrome c (cyt c).[34] Receptors for cyt c have been described [11–13, 16–18, 20–26] in addition to inhibitors of its PPIs.[35–37] The current system, however, offers significant advantages for fundamental studies of protein-surface recognition. Binding to metalloproteins and nonmetalloproteins can be detected by using simple fluorescence quenching or anisotropy changes, respectively, whilst structure–affinity studies and screening against a panel of proteins point to specific interactions with the target. Importantly, the highest affinity receptor binds cyt c with 1: 1 stoichiometry and an affinity of 2 nM.
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影响因子：
5.2
作者：
Jain, RK;Hamilton, AD
通讯作者：
Hamilton, AD
影响因子：
15
作者：
Baldini, L;Wilson, AJ;Hamilton, AD
通讯作者：
Hamilton, AD
影响因子：
4.3
作者：
Braun, M;Atalick, S;Hirsch, A
通讯作者：
Hirsch, A
影响因子：
4.9
作者：
Chiba, Fumiko;Hu, Ting-Chou;Wagstaff, Mark
通讯作者：
Wagstaff, Mark
影响因子：
5.6
作者：
KUNDROT, CE;RICHARDS, FM
通讯作者：
RICHARDS, FM