Artificial Allosteric Receptors

Kremer, Christopher; Lützen, Arne

doi:10.1002/chem.201203814

Cited by 132 publications

(97 citation statements)

References 232 publications

(457 reference statements)

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“…Many more complex multidomain regulatory proteins and biological machines that integrate multiple signaling events and long‐range coupled conformational modifications through homotropic or heterotropic binding events have shown to proceed also through allosteric mechanisms . Although the design of 3D hollow structures has led to selective receptors for guest encapsulation and promising molecular nanoreactors, their development as biomimetic allosteric receptors able to control guest complexation through large conformational changes remains a significant challenge . Such a control implies to integrate in the framework of the structure several components with defined regulation and guest binding functions.…”

Section: Introductionmentioning

confidence: 99%

Positive Allosteric Control of Guests Encapsulation by Metal Binding to Covalent Porphyrin Cages

Djemili

Kocher

Durot

et al. 2019

Chemistry A European J

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The allosteric control of the receptor properties of two flexible covalent cages is reported. These receptors consist of two zinc(II) porphyrins connected by four linkers of two different sizes, each incorporating two 1,2,3‐triazolyl ligands. Silver(I) ions act as effectors, responsible for an on/off encapsulation mechanism of neutral guest molecules. Binding silver(I) ions to the triazoles opens the cages and triggers the coordination of pyrazine or the encapsulation of N,N′‐dibutyl‐1,4,5,8‐naphthalene diimide. The X‐ray structure of the silver(I)‐complexed receptor with short connectors is reported, revealing the hollow structure with a cavity well‐defined by two eclipsed porphyrins. Rather unexpectedly, the crystallographic structure of this receptor with pyrazine as a guest molecule showed that the cavity is occupied by two pyrazines, each binding to the zinc(II) porphyrin in a monotopic fashion.

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Section: Introductionmentioning

confidence: 99%

Positive Allosteric Control of Guests Encapsulation by Metal Binding to Covalent Porphyrin Cages

Djemili

Kocher

Durot

et al. 2019

Chemistry A European J

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“…Thel iberation results from an eighboringgroup effect, which is remotely related to the dynamic allosteric effect. [37,38] Thec oupling of an output (catalysis) to the speed of am echanical motion is acharacteristic feature of machinery.As nature is using nanomechanical motions for some of its most demanding catalytic processes, [39] it should be ag reat incentive to study further links between motion and catalytic activity in nanomechanical machinery. [a] The exchange frequencies k 50 at 50 8 8Cwere calculated from the activation data.…”

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confidence: 99%

Catalytic Three‐Component Machinery: Control of Catalytic Activity by Machine Speed

et al. 2017

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Three supramolecular slider-on-deck systems DS1-DS3 were obtained as two-component aggregates from the sliders S1-S3 and deck D with its three zinc porphyrin (ZnPor) binding sites.T he binding of the two-footed slider to the deck varies with the donor qualities of and the steric hindrance at the pyridine/pyrimidine (pyr) feet, and was effected by two N pyr ! ZnPor interactions.A ccordingly,t he sliders move over the three zinc porphyrins in the deck at different speeds,n amely with 32.2, 220, and 440 kHz at room temperature.The addition of N-methylpyrrolidine as an organocatalyst to DS1-DS3 generates catalytic three-component machineries.B yu sing ac onjugate addition as ap robe reaction, we observed ac orrelation between the operating speed of the slider-ondeck systems and the yields of the catalytic reaction. As the thermodynamic binding of the slider decreases,b oth the frequency of the sliding motion and the yield of the catalytic reaction increase.The connection between protein conformational dynamics and enzymatic activity has been intensely debated [1,2] because the precise spatial arrangement and high dynamics have to work together synergistically for high turnover rates in enzymes.[3] It is thus an appealing challenge to systematically use dynamic effects in artificial catalysts to speed up ap articular process. [4,5] Herein, we describe how ad ynamic slider-on-deck system can be coupled to an organocatalyst and how the sliding speed (machine speed) in this threecomponent aggregate impacts catalysis.T he results show clearly the prevalence of kinetic over thermodynamic factors in the liberation of catalyst into solution and highlight the usefulness of dynamic multicomponent machinery.Although most biological machine archetypes are multiprotein complexes,very few examples of artificial devices [6][7][8][9][10][11][12][13][14][15][16][17][18] that arise from the self-sorting of diverse components [19][20][21] have been reported, quite in contrast to the large gamut of known covalently or topologically constructed machines. [23][24][25][26][27][28][29][30][31] Forthe present study,wechose the two-component slideron-deck systems DS1-DS3 = D·(S1-S3)( Scheme 1) for the following reasons:1)InDS1-DS3,the two-footed sliders S1-S3 should move quickly on the D 3h -symmetric deck D with its three identical zinc porphyrin (ZnPor) binding sites.2 )The speed should be adjustable by changing the binding foot of S1-S3.3 )The addition of one equiv of an organocatalyst to DS1-DS3 is expected to generate the catalytic three-component machinery cat·D·(S1-S3). 4) Thes lidersf oot (various pyridine/pyrimidine derivatives:p yr) and the organocatalyst should have comparable affinity towards the binding sites of the deck, so that liberation of the catalyst into solution may be triggered by the motion of the slider. 5) Thea mount of catalyst in solution shall be quantifiable through ac atalytic process.T hereby,s ignificantly different sliding speeds in DS1-DS3 should lead to divergent yields in the catalytic reaction.B...

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“…For these reasons, MIMs can be regarded as appealing systems for investigating allosteric communication mechanisms and implementing them within synthetic species to achieve functions (11). Nevertheless, studies of allosteric effects in rotaxanes and catenanes are rare (12) and have been limited so far to a pioneering work by Sauvage and coworkers (13) and, more recently, to the realization of stimuli-responsive switches (14,15) for controlling catalytic functions (16)(17)(18)(19)(20).…”

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confidence: 99%

Remote electrochemical modulation of pK _a in a rotaxane by co-conformational allostery

Ragazzon

Schäfer

Franchi

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Allosteric control, one of Nature's most effective ways to regulate functions in biomolecular machinery, involves the transfer of information between distant sites. The mechanistic details of such a transfer are still an object of intensive investigation and debate, and the idea that intramolecular communication could be enabled by dynamic processes is gaining attention as a complement to traditional explanations. Mechanically interlocked molecules, owing to the particular kind of connection between their components and the resulting dynamic behavior, are attractive systems to investigate allosteric mechanisms and exploit them to develop functionalities with artificial species. We show that the pK a of an ammonium site located on the axle component of a [2]rotaxane can be reversibly modulated by changing the affinity of a remote recognition site for the interlocked crown ether ring through electrochemical stimulation. The use of a reversible ternary redox switch enables us to set the pK a to three different values, encompassing more than seven units. Our results demonstrate that in the axle the two sites do not communicate, and that in the rotaxane the transfer of information between them is made possible by the shuttling of the ring, that is, by a dynamic intramolecular process. The investigated coupling of electron-and proton-transfer reactions is reminiscent of the operation of the protein complex I of the respiratory chain.acid-base processes | electrochemistry | free energy change | molecular machine | molecular switch A llostery-the process by which a chemical transformation at one site causes a change at a distant site within the same molecule or molecular assembly-is a key phenomenon for the regulation of biological activity (1, 2). A most important example is the long-range coupling of redox-active and acid-basesensitive sites, a crucial element of electron transport chains, as exemplified by the respiratory complex I (3). Although allosteric effects are usually described in terms of conformational changes induced by binding at one site directly affecting the affinity of the other site (4), the idea that the transmission of information at the basis of allostery could take place through dynamic mechanisms is receiving increasing attention (5-7). Indeed, despite its importance for life, allosteric regulation remains an elusive biochemical phenomenon.Mechanically interlocked molecules (MIMs) (8) such as rotaxanes and catenanes, because of the lack of strong chemical bonds between their molecular parts, are characterized by a rich dynamic behavior that involves changes of the relative position of the components (co-conformation). Indeed, in appropriately designed MIMs co-conformational rearrangements can be precisely controlled by modulating the noncovalent intercomponent interactions through external stimulation (9, 10). For these reasons, MIMs can be regarded as appealing systems for investigating allosteric communication mechanisms and implementing them within synthetic species to achieve functions (11)....

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Artificial Allosteric Receptors

Cited by 132 publications

References 232 publications

Positive Allosteric Control of Guests Encapsulation by Metal Binding to Covalent Porphyrin Cages

Positive Allosteric Control of Guests Encapsulation by Metal Binding to Covalent Porphyrin Cages

Catalytic Three‐Component Machinery: Control of Catalytic Activity by Machine Speed

Remote electrochemical modulation of pK _a in a rotaxane by co-conformational allostery

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Artificial Allosteric Receptors

Cited by 132 publications

References 232 publications

Positive Allosteric Control of Guests Encapsulation by Metal Binding to Covalent Porphyrin Cages

Positive Allosteric Control of Guests Encapsulation by Metal Binding to Covalent Porphyrin Cages

Catalytic Three‐Component Machinery: Control of Catalytic Activity by Machine Speed

Remote electrochemical modulation of pK a in a rotaxane by co-conformational allostery

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Remote electrochemical modulation of pK _a in a rotaxane by co-conformational allostery