Dynamische Peptide als biomimetische Kohlenhydratrezeptoren

Rauschenberg, Melanie; Bomke, Susanne; Kärst, Uwe; Ravoo, Bart Jan

doi:10.1002/ange.201002847

Cited by 24 publications

(21 citation statements)

References 44 publications

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“…These findings are in agreement with HPLC data reported previously for a dynamic combinatorial library of peptides that contain Cys-His-Cys, which displayed a higher amplification of the parallel isomer of HisHis relative to the antiparallel isomer of HisHis upon addition of NANA. [9] It can be seen in Table 1 that for each isomer of HisHis, the binding of the second molecule of NANA is considerably more favorable than the binding of the first molecule of NANA: K 2 is more than one order of magnitude larger than K 1 in each case. Binding of the second NANA is driven by a substantial increase in entropy, which likely originates from significant dehydration of both HisHis and NANA upon complexation.…”

Section: Isothermal Titration Calorimetrymentioning

confidence: 97%

“…In our previous work we had established that the mixture of HisHis isomers binds NANA in a cooperative 1:2 complex (1 molecule of HisHis binds 2 molecules of NANA) with rather strong binding constants K 1 = 70 m À1 and K 2 = 7.76 10 3 m À1 at neutral pH in water. [9] From the ITC titration of parallel HisHis (3 a) and antiparallel HisHis (7 a) with NANA, it is evident that both isomers interact with NANA in a 1:2 complex, but a significantly stronger binding of the parallel isomer is observed (see Table 1; Figure S3 in the Supporting Information). Nevertheless, both HisHis isomers are potent cooperative receptors for the binding of two equivalents of NANA in aqueous solution.…”

Section: Isothermal Titration Calorimetrymentioning

confidence: 99%

“…In our previous work we had established that the mixture of TyrTyr isomers binds with Tre in a 1:1 complex with a rather strong binding constant K a = 2.85 10 3 m À1 at neutral pH in water. [9] It was found that both isomers of TyrTyr bind with Tre with nearly the same affinity. The interaction is exothermic and entropically driven.…”

Section: Isothermal Titration Calorimetrymentioning

confidence: 99%

“…[8] In 2010, we described the identification of carbohydrate receptors from tripeptides using dynamic combinatorial chemistry and the thiol-disulfide exchange reaction under thermodynamic equilibrium. [9] We showed that the N-and C-terminal cysteine residues of tripeptides Cys-X-Cys form disulfide bonds with a second Cys-X-Cys tripeptide to yield exclusively cyclic hexapeptides (Scheme 1). The cyclic hexapeptides obtained from cysteine and histidine, Cys-His-Cys (which we call HisHis), and cysteine and tyrosine, Cys-Tyr-Cys (which we call TyrTyr), showed strong and selective interactions (K a > 1000 m À1 in aqueous solution at neutral pH) with N-acetyl neuraminic acid (NANA) and trehalose (Tre), respectively.…”

Section: Introductionmentioning

confidence: 99%

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Peptide‐Based Carbohydrate Receptors

Rauschenberg

Bandaru

Waller

et al. 2014

Chemistry A European J

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A broad spectrum of physiological processes is mediated by highly specific noncovalent interactions of carbohydrates and proteins. In a recent communication we identified several cyclic hexapeptides in a dynamic combinatorial library that interact selectively with carbohydrates with high binding constants in water. Herein, we report a detailed investigation of the noncovalent interaction of two cyclic hexapeptides (Cys-His-Cys (which we call HisHis) and Cys-Tyr-Cys (which we call TyrTyr)) with a selection of monosaccharides and disaccharides in aqueous solution. The parallel and antiparallel isomers of HisHis or TyrTyr were synthesized separately, and their interaction with monosaccharides and disaccharides in aqueous solution was studied by isothermal titration calorimetry, NMR spectroscopic titrations, and circular dichroism spectroscopy. From these measurements, we identified particularly stable complexes (Ka> 1000 M(-1)) of the parallel isomer of HisHis with N-acetylneuraminic acid and with methyl-a-d-galactopyranoside as well as of both isomers of TyrTyr with trehalose. To gain further insight into the structure of the peptide–carbohydrate complexes, structure prediction was performed using quantum chemical methods. The calculations confirm the selectivity observed in the experiments and indicate the formation of multiple intermolecular hydrogen bonds in the most stable complexes.

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Section: Isothermal Titration Calorimetrymentioning

confidence: 97%

Section: Isothermal Titration Calorimetrymentioning

confidence: 99%

Section: Isothermal Titration Calorimetrymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Peptide‐Based Carbohydrate Receptors

Rauschenberg

Bandaru

Waller

et al. 2014

Chemistry A European J

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“…Dynamic exchange reactions have been described before [27] for small molecules [27] or libraries of short peptides. [15,[28][29][30][31] We have followed such a process within a small dynamic library made of the four thiodepsipeptides 1 t , 1 t E13A , 1 t E13K , and 1 t b (95 mm each). These were equilibrated together in presence of their respective electrophilic fragments, E (200 mm), E E13A (100 mm), and E E13K (100 mm), and excess of 2mercaptoethyl sulfonate (Figure 4; Supporting Information, Figure S8).…”

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confidence: 99%

A High‐Resolution Structure that Provides Insight into Coiled‐Coil Thiodepsipeptide Dynamic Chemistry

et al. 2013

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Chemical synthesis and cell-based expression methods can afford incorporation of non-natural entities into proteins. New structures are obtained, and new functions gained, by attachment of amino acids with non-native side-chains, [1,2] modified backbones such as b-and g-amino acids, [3][4][5] or peptide bond analogues such as peptoids, esters, and thioesters. [6][7][8][9] Backbone modification with longer and flexible amino acids allows expansion of the conformational space occupied by proteins, while introduction of ester (depsipeptide) and thioester (thiodepsipeptide) bonds enhances their reactivity towards hydrolysis and other nucleophilic attacks. The durability of thioester bonds in neutral aqueous solutions and their reactivity in thiol-thioester exchange reactions make them a relevant choice for performing dynamic chemistry in water. [10][11][12][13][14][15] Particularly interesting is the possibility of utilizing such transformations for exchanging domains between different protein molecules, owing to sequence mutations or in response to chemical and physical changes.Self-organization of molecular networks has been extensively studied by scientists interested in systems chemistry. [16,17] When studying protein-based networks, it was demonstrated that the network connectivity and overall topology can be dictated by the sequence-specific information embedded in coiled-coil architectures, [18][19][20] and that careful design of the interhelical recognition interface can be used to affect the network in a predictable manner. [14,20,21] It is suggested here that the adaptive behavior of such networks, namely their rewiring in response to external triggers, can be greatly expanded if the coiled-coil proteins are formed within dynamic networks in which domain exchange readily takes place. Towards this end, we utilize coiled-coil protein analogues that contain thioester bonds within their sequences. We predict that to be mechanistically relevant for domain exchange, the thioester bond should be isostructural with the peptide bonds to maintain the 3D structure, and it should also be kept exposed and reactive towards small-molecule thiols and/or thiol-containing proteins. To highlight these characteristics, we provide here the first high-resolution structure (1.35 ) of a thioester coiled-coil protein, and compare it to the structure of the native and depsipeptide analogue proteins. The integrity of the thioester bonds and their accessibility to other molecules are revealed by analysis of the crystal structure, as well as from complementary thiolexchange assays. We then show using a set of mutants that the thioester stability can be correlated with the backbone regularity and the coiled-coil unfolding stability. Finally, a small library formed of these thioester mutants is screened for domain exchange in the absence and presence of an external template molecule, revealing significant template effect and exchange-product amplification.The sequence of the key thioester peptide (1 t ) was designed by replacing a glycin...

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