α- and β-hydrazino acid-based pseudopeptides inhibit the chymotrypsin-like activity of the eukaryotic 20S proteasome

Bordessa, Andrea; Keita, Massaba; Maréchal, Xavier; Formicola, Lucia; Lagarde, Nathalie; Rodrigo, Jordi; Bernadat, Guillaume; Bauvais, Cyril; Soulier, Jean-Louis; Dufau, Laure; Milcent, Thierry; Crousse, Benoı̂t; Reboud‐Ravaux, Michèle; Ongeri, Sandrine

doi:10.1016/j.ejmech.2013.09.059

Cited by 19 publications

(24 citation statements)

References 47 publications

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“…Also, intramolecular hydrogen bonding pattern in such peptidomimetics promotes formation of unique secondary structure, known as hydrazino-turn (Acherar et al 2013 ; Salaün et al 2006; Cheguillaume et al 2001 ). Hydrazino-based peptidomimetics show promising biological activities, like protease inhibition (Bordessa et al 2013 ; Aubin et al 2005 ) and antimicrobial activity (Laurencin et al 2012a , b ). It is therefore important to have a method for fast and easy construction of such templates.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of hybrid hydrazino peptides: protected vs unprotected chiral α-hydrazino acids

Suć

Jerić

2015

SpringerPlus

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Peptidomimetics based on hydrazino derivatives of α-amino acids represent an important class of peptidic foldamers with promising biological activities, like protease inhibition and antimicrobial activity. However, the lack of straightforward method for the synthesis of optically pure hydrazino acids and efficient incorporation of hydrazino building blocks into peptide sequence hamper wider exploitation of hydrazino peptidomimetics. Here we described the utility of Nα-benzyl protected and unprotected hydrazino derivatives of natural α-amino acids in synthesis of peptidomimetics. While incorporation of Nα-benzyl-hydrazino acids into peptide chain and deprotection of benzyl moiety proceeded with difficulties, unprotected hydrazino acids allowed fast and simple construction of hybrid peptidomimetics.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-015-1288-9) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Synthesis of hybrid hydrazino peptides: protected vs unprotected chiral α-hydrazino acids

Suć

Jerić

2015

SpringerPlus

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“…Fortunately,t he Rh-nitrene insertedinto the sulfonamide linkagethrough SÀNbond cleavage to provide 5a-c in moderate yields (40-51 %, Ta ble3), althougha dditional catalyst( 4mol %) and reagents were required for complete consumption of the substrate. [25] To demonstrate the practicality of the formal nitrene insertion into an amide bond, we performed the reaction with the short peptide 6,w hicha fforded 7 with an a-hydrazino amide unit, [26] whichh as been widely appliedi nm edicinal andp harmaceutical chemistry as ap roteasome inhibitor, [27] antimicrobial agent, [28] and DNA/RNA interactor [29] (Scheme 2).…”

Section: Resultsmentioning

confidence: 99%

Chemoselective Intramolecular Formal Insertion Reaction of Rh–Nitrenes into an Amide Bond Over C−H Insertion

Kono

Harada

Nemoto

2019

Chemistry A European J

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The past few decades have witnessed extensive efforts to discloset he unique reactivity of metal-nitrenes, because they could be ap owerful synthetic tool for introducing the amine functionality into unactivated chemical bonds. The reactivity of metal-nitrenes, however,i sc urrently mainly confined to aziridination (an insertion into aC =C bond) and CÀHa mination (an insertion into aC ÀHb ond). Nitrene insertion into an amide CÀNb ond, however,h as not been reported so far.I nt his work we have developedarhodium-catalyzed one-nitrogen insertion into amide CÀNa nd sulfonamideS ÀNb onds. Experimental and theoretical analy-ses based on density functional theory indicate that the formal amide insertion proceeds via ar hodium-coordinated ammonium ylide formed between the nitrene and the amide nitrogen, followed by acyl group transfer concomitant with CÀNb ond cleavage. Mechanistic studies have allowed rationalization of the origin of the chemoselectivity observed between the CÀHa nd amide insertion reactions. The methodology presented herein is the first example of an insertion of nitrene into amide bonds and provides facile access to unique diazacyclic systems with an NÀNb ond linkage.Scheme1.Reactions leadingt oN + ÀN À ylide formation from metal-nitrenes.Supporting information and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

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“…An enhanced ChT-L inhibitory activity was observed when the P3 methyl group affected whereas the C-L one was very poorly inhibited only for compound 5c. The CO(4-BnO)C 6 H 4 N-terminal blocking group known to potentially occupy small accessory hydrophobic pockets AS1 and AS2 [18,25] led to efficient and selective ChT-L inhibition (5f and 5e). This effect was increased by more than one order of magnitude when the R 3 alanine group (5e) was replaced with the threonine residue (5f).…”

Section: In Vitro Inhibition Studiesmentioning

confidence: 99%

“…Several peptides are noncovalent inhibitors [9], such as the natural TMC-95A and its cyclic and linear mimics 1a and 2a [10][11][12][13][14][15][16][17], dipeptides (e.g. 3-4) [18][19][20][21][22][23][24], and pseudopeptides [25][26][27] (Figure 2). Nonpeptidic noncovalent inhibitors have also been described (e. g. sulfonamides [28][29][30][31], hydroxyurea [32], 1,2,4-oxadiazoles [33], pyrazoles [34], phakellins [35], quinolines [36], psoralene [37]).…”

Section: Introductionmentioning

confidence: 99%

Structure-based design of human immuno- and constitutive proteasomes inhibitors

Richy

Sarraf

Maréchal

et al. 2018

European Journal of Medicinal Chemistry

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Starting from the X-ray structure of our previous tripeptidic linear mimics of TMC-95A in complex with yeast 20S proteasome, we introduced new structural features to induce a differential inhibition between human constitutive and immunoproteasome 20S particles. Libraries of 24 tripeptidic and 6 dipeptidic derivatives were synthesized. The optimized preparation of 3-hydroxyoxindolyl alanine residues from tryptophan and their incorporation in peptides were described. Several potent inhibitors of human constitutive proteasome and immunoproteasome acting at the nanomolar level (IC = 7.1 nM against the chymotrypsin-like activity for the best inhibitor) were obtained. A cytotoxic effect at the submicromolar level was observed against 6 human cancer cell lines.

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α- and β-hydrazino acid-based pseudopeptides inhibit the chymotrypsin-like activity of the eukaryotic 20S proteasome

Cited by 19 publications

References 47 publications

Synthesis of hybrid hydrazino peptides: protected vs unprotected chiral α-hydrazino acids

Synthesis of hybrid hydrazino peptides: protected vs unprotected chiral α-hydrazino acids

Chemoselective Intramolecular Formal Insertion Reaction of Rh–Nitrenes into an Amide Bond Over C−H Insertion

Structure-based design of human immuno- and constitutive proteasomes inhibitors

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