Rapid biocompatible macrocyclization of peptides with decafluoro-diphenylsulfone

Kalhor-Monfared, Shiva; Jafari, Mohammad Reza; Patterson, James T.; Kitov, Pavel I.; Dwyer, John J.; Nuss, John M.; Derda, Ratmir

doi:10.1039/c5sc03856a

Cited by 89 publications

(96 citation statements)

References 43 publications

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“…Moreover,t he low solubility of previously described perfluoroaryl reagents ( Figure 13) limits their utility in aqueous solutions.Inanattempt to use perfluoroarenes in aqueous media, Derda in 2016 identified decafluorobiphenylsulfone as av ery reactive electrophile for the arylation of cysteine thiol under aqueous conditions. [122] A reaction rate of 180 m À1 s À1 was observed when treating ap entapeptide (Ser-Trp-Cys-Arg-Cys) with decafluorobiphenylsulfone in Tr is buffer (pH 8.5) with 40 %a cetonitrile. Thei ncreased reactivity of decafluorobiphenylsulfone in aqueous media enabled its application for the modification of biomolecules sensitive to organic solvents.U sing this reagent, Derda macrocyclized peptide libraries displayed on the surface of the M13 phage with good efficiency (Figure 16).…”

Section: Perfluoroarenes For Cysteine Arylationmentioning

confidence: 99%

Arylation Chemistry for Bioconjugation

et al. 2019

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Bioconjugation chemistry has been used to prepare modified biomolecules with functions beyond what nature intended. Central to these techniques is the development of highly efficient and selective bioconjugation reactions that operate under mild, biomolecule compatible conditions. Methods that form a nucleophile–sp2 carbon bond show promise for creating bioconjugates with new modifications, sometimes resulting in molecules with unparalleled functions. Here we outline and review sulfur, nitrogen, selenium, oxygen, and carbon arylative bioconjugation strategies and their applications to modify peptides, proteins, sugars, and nucleic acids

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Section: Perfluoroarenes For Cysteine Arylationmentioning

confidence: 99%

Arylation Chemistry for Bioconjugation

et al. 2019

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“…Interestingly, reports of sulfur nucleophiles reacting with pentafluoropyridine (1) are not well document in the literature. [14][15][16] Substituents will affect the reactivity of 1 towards nucleophilic attack and to probe this, aniline variants of 1 where investigated as electrophiles in the reaction with pep1. Electrophiles 8-10 (Table 1) displayed significantly different reactivity profiles to 1, as exemplified by 4-aminotetrafluoropyridine (8), which was found to be completely unreactive ( Table 1, entry 3 and ESI Fig.…”

Section: Exploring the Scope Of Perfluoroaromatics For The S N Ar-tagmentioning

confidence: 99%

The application of perfluoroheteroaromatic reagents in the preparation of modified peptide systems

et al. 2017

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The perfluoroheteroaromatic reagent pentafluoropyridine has proved to be a highly reactive electrophile, undergoing SAr arylation reactions in the presence of a range of nucleophilic peptide side chains (i.e. cysteine, tyrosine, serine and lysine) under mild conditions. Moreover, we have shown how one-step peptide-modification using perfluoroheteroaromatics can deliver enhanced proteolytic stability in pharmaceutically-relevant peptides such as oxytocin.

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“…To test whether cluster 3 exhibits enhanced SNAr reactivity toward thiols, we exposed 3 dissolved in DMF to a stoichiometric amount of an unprotected thiolated saccharide, 1-thio-β-Dglucose sodium salt, and observed by 19 F NMR spectroscopy a nearly quantitative (≥99%) conversion to 3c ( Table 1, water. 49 Overall, these studies demonstrate that by employing rational linker design, the SNAr reaction characteristics including kinetics and aqueous compatibility can be dramatically enhanced, allowing for the rapid assembly of atomically precise, densely glycosylated nanomolecules.…”

Section: Table 1 Glycosylation and Pegylation Of Clusters 2 Andmentioning

confidence: 82%

Multivalent Cluster Nanomolecules for Inhibiting Protein-Protein Interactions

Qian¹,

Han²,

Messina³

et al. 2019

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Multivalent protein-protein interactions serve central roles in many essential biological processes, ranging from cell signaling and adhesion to pathogen recognition. Uncovering the rules that govern these intricate interactions is important not only to basic biology and chemistry, but also to the applied sciences where researchers are interested in developing molecules to promote or inhibit these interactions. Here we report the synthesis and application of atomically precise inorganic cluster nanomolecules consisting of an inorganic core and a covalently linked densely packed layer of saccharides. These hybrid agents are stable under biologically relevant conditions and exhibit multivalent binding capabilities, which enable us to study the complex interactions between glycosylated structures and a dendritic cell lectin receptor. Importantly, we find that subtle changes in the molecular structure lead to significant differences in the nanomolecule’s protein binding properties. Furthermore, we demonstrate an example of using these hybrid nanomolecules to effectively inhibit protein-protein interactions in a human cell line. Ultimately, this work reveals an intricate interplay between the structural design of multivalent agents and their biological activities toward protein surfaces.

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Rapid biocompatible macrocyclization of peptides with decafluoro-diphenylsulfone

Abstract: In this manuscript, we describe modification of Cys-residues in peptides and proteins in aqueous solvents via aromatic nucleophilic substitution (SNAr) with perfluoroarenes (fAr).

Cited by 89 publications

References 43 publications

Arylation Chemistry for Bioconjugation

Arylation Chemistry for Bioconjugation

The application of perfluoroheteroaromatic reagents in the preparation of modified peptide systems

Multivalent Cluster Nanomolecules for Inhibiting Protein-Protein Interactions

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