Stepwise triple-click functionalization of synthetic peptides

Ковальова, А. М.; Pohl, Radek; Vrábel, Milan

doi:10.1039/c8ob01617h

Cited by 12 publications

(4 citation statements)

References 30 publications

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“…Con A can be readily obtained from natural sources (jack‐bean) in large quantities and is also commercially available, making it an ideal candidate for our proof‐of‐concept study. Based on our previous work, [16] we constructed a one‐bead‐one‐compound (OBOC) glycopeptide library. This library was carefully designed to contain α‐ d ‐mannose‐ and α‐ d ‐glucose moieties at defined positions.…”

Section: Resultsmentioning

confidence: 99%

Selection of Galectin‐Binding Ligands from Synthetic Glycopeptide Libraries

Kovalová,

Prouza,

Zavřel

et al. 2023

ChemPlusChem

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Galectins, a class of carbohydrate‐binding proteins, play a crucial role in various physiological and disease processes. Therefore, the identification of ligands that efficiently bind these proteins could potentially lead to the development of new therapeutic compounds. In this study, we present a method that involves screening synthetic click glycopeptide libraries to identify lectin‐binding ligands with low micromolar affinity. Our methodology, initially optimized using Concanavalin A, was subsequently applied to identify binders for the therapeutically relevant galectin 1. Binding affinities were assessed using various methods and showed that the selected glycopeptides exhibited enhanced binding potency to the target lectins compared to the starting sugar moieties. This approach offers an alternative means of discovering galectin‐binding ligands as well as other carbohydrate‐binding proteins, which are considered important therapeutic targets.

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Section: Resultsmentioning

confidence: 99%

Selection of Galectin‐Binding Ligands from Synthetic Glycopeptide Libraries

Kovalová,

Prouza,

Zavřel

et al. 2023

ChemPlusChem

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“…There is a significant interest in developing bioorthogonal chemistry that allows targeting more than one position individually. [57][58][59][60] The finding that bulky tert-butyl groups increase the rate of the isonitriletetrazine reaction while effectively blocking the approach of alkene-based dienophiles naturally allows for developing orthogonal reactant pairs. Leeper et al had already shown previously that isonitriles are orthogonal to azide-alkyne reactions.…”

Section: Account Syn Lettmentioning

confidence: 99%

The Unique Bioorthogonal Chemistry of Isonitriles

Deb¹,

Franzini²

2020

Synlett

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The isocyano group is the structurally most compact bioorthogonal group known. It reacts with tetrazines under physiological conditions and has great potential for widespread use in the biosciences. In this account, we highlight the unique properties of the isocyano group as a bioorthogonal functionality. Protecting group chemistry based on the reaction of isonitriles and tetrazines that allows releasing payloads is a particular focus of the article. We further discuss the atypical steric attractions that take place in the transition state of the reaction between isonitriles and tetrazines, which result in an increase in the rate of the reaction with steric bulk of the tetrazine substituents. These findings will open up new possibilities in bioorthogonal chemistry where reactivity and stability are simultaneously desired.1 Introduction2 The Isocyano Group: A Structurally Compact Group for Bioorthogonal Chemistry3 Bioorthogonal Protecting Group Chemistry4 Steric Attractions in the Transition State Accelerate the Cycloaddition of Isonitriles and Tetrazines5 Reactions of Tetrazines and Isonitriles are Compatible with Biomolecules and Living Organisms6 Conclusions

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“…Noteworthy, the preparation of peptide-based bioimaging probes can take advantage of the rich chemical toolbox of peptide chemistry that enables their straightforward synthesis and functionalization, strongly expanding their potential applications and utility. Peptide functionalization is usually performed in solid phase during on-resin peptide synthesis, and it often requires complex orthogonal protection/deprotection schemes. − Peptide functionalization in solid phase, although ensuring a high level of specificity, usually proceeds under harsh conditions, and it is not always well tolerated by the imaging moieties; furthermore, it is expensive due to the consumption of large excesses of precious reactants and it is not environmentally sustainable, being that the synthetic steps are completely performed in organic solvents. The development of cost-effective and greener chemical procedures enabling the site-specific functionalization of peptide sequences under mild conditions is strongly desired to further the effective wide spreading of peptide-probes in bioimaging.…”

Section: Introductionmentioning

confidence: 99%

A Chemical Strategy for the Preparation of Multimodified Peptide Imaging Probes

et al. 2023

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Multimodality probes appear of great interest for innovative imaging applications in disease diagnosis. Herein, we present a chemical strategy enabling site-specific double-modification and cyclization of a peptide probe exploiting native chemical ligation (NCL) and thiol-maleimide addition. The synthetic strategy is straightforward and of general applicability for the development of double-labeled peptide multimodality probes.

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Stepwise triple-click functionalization of synthetic peptides

Abstract: A sequence of click reactions and selective deprotection steps enables the stepwise synthesis of defined triple-functionalized peptides.

Cited by 12 publications

References 30 publications

Selection of Galectin‐Binding Ligands from Synthetic Glycopeptide Libraries

Selection of Galectin‐Binding Ligands from Synthetic Glycopeptide Libraries

The Unique Bioorthogonal Chemistry of Isonitriles

A Chemical Strategy for the Preparation of Multimodified Peptide Imaging Probes

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