Catalysis of Hydrazone and Oxime Peptide Ligation by Arginine

Ollivier, Nathalie; Agouridas, Vangelis; Snella, Benoît; Desmet, Rémi; Drobecq, Hervé; Vicogne, Jérôme; Melnyk, Oleg

doi:10.1021/acs.orglett.0c03195

Cited by 6 publications

(4 citation statements)

References 32 publications

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“…The model cross-linking reaction between the nucleoside 2′-deoxyguanosine and 3 was carried out in a solvent mixture composed of 1:5 DMSO and HEPES buffer (50 mM, pH 7.4) containing arginine as a catalyst. , Chemical precedents provided by the reactions of 2′-deoxyguanosine with low molecular weight α,β-unsaturated aldehydes enabled us to suspect that this reaction would proceed via aza-Michael-type addition of the exocyclic N 2 -amino group of the guanine residue to the α,β-unsaturated sugar residue. ,, LC-MS analysis of the reaction revealed a mixture of isomeric products displaying the [M + H] + ion (at m / z 384 amu) anticipated for the nucleosidic ICL model 4 (Scheme ). NMR analyses of this mixture revealed signals consistent with 4 , but detailed assignment of the resonances was not possible due to the complexity of the spectra (up to 14 equilibrating isomers are possible for this product, four diastereomers of the O-cyclized pyranose form, four diastereomers of the O-cyclized furanose form, four diastereomers of the N-cyclized form, and two enantiomers of the ring-opened form).…”

Section: Resultssupporting

confidence: 56%

Formation and Repair of an Interstrand DNA Cross-Link Arising from a Common Endogenous Lesion

et al. 2021

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Interstrand DNA cross-links (ICLs) are cytotoxic because they block the strand separation required for read-out and replication of the genetic information in duplex DNA. The unavoidable formation of ICLs in cellular DNA may contribute to aging, neurodegeneration, and cancer. Here, we describe the formation and properties of a structurally complex ICL derived from an apurinic/apyrimidinic (AP) site, which is one of the most common endogenous lesions in cellular DNA. The results characterize a cross-link arising from aza-Michael addition of the N 2-amino group of a guanine residue to the electrophilic sugar remnant generated by spermine-mediated strand cleavage at an AP site in duplex DNA. An α,β-unsaturated iminium ion is the critical intermediate involved in ICL formation. Studies employing the bacteriophage φ29 polymerase provided evidence that this ICL can block critical DNA transactions that require strand separation. The results of biochemical studies suggest that this complex strand break/ICL might be repaired by a simple mechanism in which the 3′-exonuclease action of the enzyme apurinic/apyrimidinic endonuclease (APE1) unhooks the cross-link to initiate repair via the single-strand break repair pathway.

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Section: Resultssupporting

confidence: 56%

Formation and Repair of an Interstrand DNA Cross-Link Arising from a Common Endogenous Lesion

et al. 2021

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“…The kinetic data could be fitted to an apparent second-order rate law (dashed lines). Based on the obtained rate constants, hydrazone formation proceeds ~3 times faster with the peptide reactants equipped with the charged modules ( 13a,a vs 13d,g ) when the catalyst is arginine (50 mM) 40 , and 13 times faster with aniline catalyst used at the same concentration. Another series of experiments were performed using a larger diversity of charged peptide modules and arginine as catalyst to enable the monitoring of hydrazone formation by UV spectroscopy (see Supplementary Methods, Supplementary Figs.…”

Section: Resultsmentioning

confidence: 99%

“…The reactions were conducted in phosphate buffer (50 mM) at neutral pH, in the presence of aniline 26 , 27 , 39 or arginine 40 acting as nucleophilic catalysts. The results of the kinetic study are presented in Fig.…”

Section: Resultsmentioning

confidence: 99%

A biomimetic electrostatic assistance for guiding and promoting N-terminal protein chemical modification

et al. 2022

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The modification of protein electrostatics by phosphorylation is a mechanism used by cells to promote the association of proteins with other biomolecules. In this work, we show that introducing negatively charged phosphoserines in a reactant is a powerful means for directing and accelerating the chemical modification of proteins equipped with oppositely charged arginines. While the extra charged amino acid residues induce no detectable affinity between the reactants, they bring site-selectivity to a reaction that is otherwise devoid of such a property. They also enable rate accelerations of four orders of magnitude in some cases, thereby permitting chemical processes to proceed at the protein level in the low micromolar range, using reactions that are normally too slow to be useful in such dilute conditions.

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“…Formation of AP-derived ICLs likely proceeds via an imine intermediate (Figure A). Therefore, we examined whether inclusion of established imine-formation catalysts aniline (1 mM), , anthranilic acid (100 mM), arginine (1 mM), and N , N ′-dimethylethylenediamine (DMEDA, 20 mM) increased the rate of ICL formation in the AP-containing duplex 1a . We found that none of these agents served as effective catalysts for dA-AP cross-link formation (Table ).…”

Section: Resultsmentioning

confidence: 99%

Effects of Local Sequence, Reaction Conditions, and Various Additives on the Formation and Stability of Interstrand Cross-Links Derived from the Reaction of an Abasic Site with an Adenine Residue in Duplex DNA

et al. 2022

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The experiments described here examined the effects of reaction conditions, various additives, and local sequence on the formation and stability interstrand cross-links (ICLs) derived from the reaction of an apurinic/apyrimidinic (AP) site with the exocyclic amino group of an adenine residue on the opposing strand in duplex DNA. Cross-link formation was observed in a range of different buffers, with faster formation rates observed at pH 5. Inclusion of the base excision repair enzyme alkyladenine DNA glycosylase (hAAG) which binds tightly to AP-containing duplexes decreased, but did not completely prevent, formation of the dA-AP ICL. Formation of the dA-AP ICL was not altered by the presence of the biological metal ion Mg 2+ or the biological thiol, glutathione. Several organocatalysts of imine formation did not enhance the rate of dA-AP ICL formation. Duplex length did not have a large effect on dA-AP yield, so long as the melting temperature of the duplex was not significantly below the reaction temperature (the duplex must remain hybridized for efficient ICL formation). Formation of the dA-AP ICL was examined in over 40 different sequences that varied the neighboring and opposing bases at the cross-linking site. The results indicate that ICL formation can occur in a wide variety of sequence contexts under physiological conditions. Formation of the dA-AP ICL was strongly inhibited by the aldehyde-trapping agents methoxyamine and hydralazine, by NaBH 3 CN, by the intercalator ethidium bromide, and by the minor groove-binding agent netropsin. ICL formation was inhibited to some extent in bicarbonate and Tris buffers. The dA-AP ICL showed substantial inherent stability under a variety of conditions and was not a substrate for AP-processing enzymes APE1 or Endo IV. Finally, we characterized cross-link formation in a small (11 bp) stem-loop (hairpin) structure and in DNA-RNA hybrid duplexes.

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Catalysis of Hydrazone and Oxime Peptide Ligation by Arginine

Cited by 6 publications

References 32 publications

Formation and Repair of an Interstrand DNA Cross-Link Arising from a Common Endogenous Lesion

Formation and Repair of an Interstrand DNA Cross-Link Arising from a Common Endogenous Lesion

A biomimetic electrostatic assistance for guiding and promoting N-terminal protein chemical modification

Effects of Local Sequence, Reaction Conditions, and Various Additives on the Formation and Stability of Interstrand Cross-Links Derived from the Reaction of an Abasic Site with an Adenine Residue in Duplex DNA

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