Photoisomerization-enhanced 1,3-dipolar cycloaddition of carbon-bridged octocyclic azobenzene with photo-released nitrile imine for peptide stapling and imaging in live cells

A novel photo-click ligation reaction between nitrile imines and photo-switchable octocyclic azobenzenes was established to both tune the conformation of the NoxaB peptide and conjugate probes with enhanced efficacy in cell apoptosis.

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π-Facial Selectivity in 1,3-Dipolar Cycloaddition Reactions of α-Methylidene-γ-lactone Substituted by 4-Methyl-2,6,7-trioxabicyclo[2.2.2]octan-1-yl Group in γ-Position

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc20020353 ◽

2002 ◽

Vol 67 (3) ◽

pp. 353-364 ◽

Cited By ~ 3

Author(s):

Petr Melša ◽

Ctibor Mazal

Keyword(s):

Double Bond ◽

Carboxylic Acid ◽

Nitrile Oxide ◽

Dipolar Cycloaddition ◽

Cycloaddition Reactions ◽

Enantiomerically Pure ◽

Nitrile Imine ◽

Facial Selectivity ◽

Excellent Selectivity

Diastereoselectivity of 1,3-dipolar cycloaddition reactions of benzyl azide, diazomethane, a nitrile oxide and a nitrile imine to α-methylidene-γ-lactone dipolarophile was effectively controlled by a bulky γ-substituent, 4-methyl-2,6,7-trioxabicyclo[2.2.2]octan-1-yl in γ-position of the dipolarophile. The dipoles added from the less hindered face of the double bond with an excellent selectivity. Enantiomerically pure dipolarophile was prepared from the easily available (S)-5-oxotetrahydrohydrofuran-2-carboxylic acid.

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The Quest for Carbenic Nitrile Imines: Experimental and Computational Characterization ofC-Amino Nitrile Imine

European Journal of Organic Chemistry ◽

10.1002/ejoc.201501153 ◽

2015 ◽

Vol 2015 (34) ◽

pp. 7484-7493 ◽

Cited By ~ 21

Author(s):

Cláudio M. Nunes ◽

Igor Reva ◽

Mário T. S. Rosado ◽

Rui Fausto

Keyword(s):

Nitrile Imine ◽

Nitrile Imines ◽

Amino Nitrile

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A Physical Organic Approach to Tuning Reagents for Selective and Stable Methionine Bioconjugation

10.26434/chemrxiv.8176823.v1 ◽

2019 ◽

Cited By ~ 1

Author(s):

Alec Christian ◽

Shang Jia ◽

Patricia Zhang ◽

Arismel Tena Meza ◽

Matthew S. Sigman ◽

...

Keyword(s):

Structural Features ◽

Data Driven ◽

Live Cells ◽

Design And Synthesis ◽

Use Of Data ◽

Physical Organic ◽

Driving Stability ◽

Peptide Stapling ◽

Insight Into ◽

Unique Chemical

We report a data-driven, physical organic approach to the development of new methionine-selective bioconjugation reagents with tunable adduct stabilities. Statistical modeling of structural features described by intrinsic physical organic parameters was applied to the development of a predictive model and to gain insight into features driving stability of adducts formed from the chemoselective coupling of oxaziridine and methionine thioether partners through Redox Activated Chemical Tagging (ReACT). From these analyses, a correlation between sulfimide stabilities and sulfimide  (C=O) stretching frequencies was revealed. We ex-ploited the rational gains in adduct stability exposed by this analysis to achieve the design and synthesis of a bis-oxaziridine reagent for peptide stapling. Indeed, we observed that a macrocyclic peptide formed by ReACT stapling at methionine exhibited improved uptake into live cells compared to an unstapled congener, highlighting the potential utility of this unique chemical tool for thioether modification. This work provides a template for the broader use of data-driven approaches to bioconjugation chemistry and other chemical biology applications.

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