High Affinity Recognition of a Selected Amino Acid Epitope within a Protein by Cucurbit[8]uril Complexation

Sonzini, Silvia; Marcozzi, Alessio; Gübeli, Raphael J.; Walle, Christopher F. van der; Ravn, Peter; Herrmann, Andreas; Scherman, Oren A.

doi:10.1002/anie.201606763

Cited by 57 publications

(49 citation statements)

References 35 publications

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“…Many materials have been used to construct peptide receptors including macrocycles 1,3 such as cyclodextrin 2,4 and cucurbituril, 8,10,12 amide oligomers 1,6,7,9,11 and self-assembled nanocages. 5 Molecularly imprinted polymers 15–20 have also been employed.…”

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confidence: 99%

Sequence-Selective Binding of Oligopeptides in Water through Hydrophobic Coding

2017

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A general method for sequence-specific binding of peptides remains elusive despite decades of research. By creating an array of “hydrophobically coded dimples” on the surface of a surface–core doubly cross-linked micelle, we synthesized water-soluble nanoparticle receptors to recognize peptides by the location, number, and nature of their hydrophobic side chains. Minute differences in the side chains could be distinguished and affinities up to 20 nM were obtained for biologically active oligopeptides in water.

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confidence: 99%

Sequence-Selective Binding of Oligopeptides in Water through Hydrophobic Coding

2017

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“…For our antidote approach to be realized in vivo , it will require highly stable reactants with strict specificity, faster reactivity, and nearly complete efficiency. Solutions may include alternative click chemistry options such as the inverse Diels-Alders reaction using a tetrazine and trans -cyclooctene (34, 35) or potentially very high affinity non-covalent interactions (36). However, each of these technologies will need to be examined in the context of non-natural amino acid incorporation into the therapeutic antibody and reaction specificity in serum.…”

Section: Discussionmentioning

confidence: 99%

An antidote approach to reduce risk and broaden utility of antibody-based therapeutics

Portnoff¹,

Gao²,

Borrok³

et al. 2017

Journal of Biological Chemistry

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Antibody therapeutics offer effective treatment options for a broad range of diseases. One of the greatest benefits of antibody therapeutics is their extraordinarily long serum half-life, allowing infrequent dosing with long-lasting effects. A characteristic of antibodies that drives long half-life is the ability to interact with the recycling receptor, FcRn, in a pH-dependent manner. The benefit of long half-life, however, carries with it liabilities. Although the positive effects of antibody therapeutics are long-lasting, any acute adverse events or chronic negative impacts, such as immunosuppression in the face of an infection, are also long-lasting. Therefore, we sought to develop antibodies with a chemical handle that alone would enjoy the long half-life of normal antibodies but, upon addition of a small-molecule antidote, would interact with the chemical handle and inhibit the antibody recycling mechanism, thus leading to rapid degradation and shortened half-life in vivo. Here we present a proof of concept study where we identify sites to incorporate a non-natural amino acid that can be chemically modified to modulate FcRn interaction in vitro and antibody half-life in vivo. This is an important first step in developing safer therapeutics, and the next step will be development of technology that can perform the modifying chemistry in vivo.

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“…It can therefore help understanding the recognition and selectivity for biological systems 11. Cucurbit[ n ]uril (CB n ), a pumpkin‐shaped synthetic macrocycle,12 represents an attractive host for supramolecular interactions 13. The CB n molecule can complex with a range of guests due to its hydrophobic cavities and two hydrophilic carbonylated rims 14.…”

Section: Introductionmentioning

confidence: 99%

The Cucurbit[7]Uril‐Based Supramolecular Chemistry for Reversible B/Z‐DNA Transition

Wang

et al. 2018

Advanced Science

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As a left‐handed helical structure, Z‐DNA is biologically active and it may be correlated with transcription and genome stability. Until recently, it remained a significant challenge to control the B/Z‐DNA transition under physiological conditions. The current study represents the first to reversibly control B/Z‐DNA transition using cucurbit[7]uril‐based supramolecular approach. It is demonstrated that cucurbit[7]uril can encapsulate the central butanediamine moiety [HN(CH2)4NH] and reverses Z‐DNA caused by spermine back to B‐DNA. The subsequent treatment with 1‐adamantanamine disassembles the cucurbit[7]uril/spermine complex and readily induces reconversion of B‐ into Z‐DNA. The DNA conformational change is unequivocally demonstrated using different independent methods. Direct evidence for supramolecular interactions involved in DNA conformational changes is further provided. These findings can therefore open a new route to control DNA helical structure in a reversible way.

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High Affinity Recognition of a Selected Amino Acid Epitope within a Protein by Cucurbit[8]uril Complexation

Cited by 57 publications

References 35 publications

Sequence-Selective Binding of Oligopeptides in Water through Hydrophobic Coding

Sequence-Selective Binding of Oligopeptides in Water through Hydrophobic Coding

An antidote approach to reduce risk and broaden utility of antibody-based therapeutics

The Cucurbit[7]Uril‐Based Supramolecular Chemistry for Reversible B/Z‐DNA Transition

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