Cyclopropenone Research Articles

Site-Specific Quadruple-Functionalised Antibodies.

Antibody-drug conjugates (ADCs) are a growing class of chemotherapeutic agents that have yielded striking clinical successes. However, the efficacy of ADCs often suffers from issues associated with tumor heterogeneity and resistance. To overcome these problems, a new generation of ADCs comprising a single monoclonal antibody with multiple different payloads attached, termed multi-payload ADCs, have been developed. Here we deploy multiple orthogonal site-specific protein modification strategies to generate highly homogeneous multi-functionalised antibody conjugates comprising up to four different functionalities installed at four unique sites on the antibody. This work, which includes the use of a site-specific cyclopropenone (CPO)-based reagent, represents the first example of a homogeneous multi-payload ADC with a payload count greater than two, and thereby facilitates the development of the next generation of ADCs.

Site‐Specific Quadruple‐Functionalised Antibodies

AbstractAntibody–drug conjugates (ADCs) are a growing class of chemotherapeutic agents that have yielded striking clinical successes. However, the efficacy of ADCs often suffers from issues associated with tumor heterogeneity and resistance. To overcome these problems, a new generation of ADCs comprising a single monoclonal antibody with multiple different payloads attached, termed multi‐payload ADCs, have been developed. Here we deploy multiple orthogonal site‐specific protein modification strategies to generate highly homogeneous multi‐functionalised antibody conjugates comprising up to four different functionalities installed at four unique sites on the antibody. This work, which includes the use of a site‐specific cyclopropenone (CPO)‐based reagent, represents the first example of a homogeneous multi‐payload ADC with a payload count greater than two, and thereby facilitates the development of the next generation of ADCs.

Platform for Orthogonal N-Cysteine-Specific Protein Modification Enabled by Cyclopropenone Reagents.

Protein conjugates are valuable tools for studying biological processes or producing therapeutics, such as antibody–drug conjugates. Despite the development of several protein conjugation strategies in recent years, the ability to modify one specific amino acid residue on a protein in the presence of other reactive side chains remains a challenge. We show that monosubstituted cyclopropenone (CPO) reagents react selectively with the 1,2-aminothiol groups of N-terminal cysteine residues to give a stable 1,4-thiazepan-5-one linkage under mild, biocompatible conditions. The CPO-based reagents, all accessible from a common activated ester CPO-pentafluorophenol (CPO-PFP), allow selective modification of N-terminal cysteine-containing peptides and proteins even in the presence of internal, solvent-exposed cysteine residues. This approach enabled the preparation of a dual protein conjugate of 2×cys-GFP, containing both internal and N-terminal cysteine residues, by first modifying the N-terminal residue with a CPO-based reagent followed by modification of the internal cysteine with a traditional cysteine-modifying reagent. CPO-based reagents enabled a copper-free click reaction between two proteins, producing a dimer of a de novo protein mimic of IL2 that binds to the β-IL2 receptor with low nanomolar affinity. Importantly, the reagents are compatible with the common reducing agent dithiothreitol (DTT), a useful property for working with proteins prone to dimerization. Finally, quantum mechanical calculations uncover the origin of selectivity for CPO-based reagents for N-terminal cysteine residues. The ability to distinguish and specifically target N-terminal cysteine residues on proteins facilitates the construction of elaborate multilabeled bioconjugates with minimal protein engineering.

Silver-catalyzed ring-opening [3+2] annulation of cyclopropenones with amides

A silver(i)-catalyzed ring-opening [3+2] annulation between cyclopropenones and amides has been achieved to afford 5-amino-2-furanones.

Aryne’t You Doubly Impressed with this Cyclopropenone Insertion?

Aryne’t You Doubly Impressed with this Cyclopropenone Insertion?

Practicality in using diphenyl cyclo propenone for alopecia areata

Diphenyl cyclo propenone (DPCP) is used as a topical immunomodulator in alopecia areata. It is a potent allergen. The process of procuring, dilution and application limits its wider use. This short communication aims to make the DPCP application easy to use.

Experiments show cyclopropenone is aromatic

Experiments show cyclopropenone is aromatic

Additionsreaktionen von 2-Amino-1-azetinen mit Cyclopropenonen; Bildung von Azepinderivaten durch Ringerweiterung

Addition Reactions of 2-Amino-1-azetines with Cyclopropenones; Formation of Azepine Derivatives by Ring Expansion Reactions. The reaction of 2-amino-1-azetines of type 6 with 2,3-diphenylcyclopropenone (1a) in acetonitrile leads to azeto[1,2-a]pyrroles (cf: 7 and 9, Schemes 3 and 4) in good yield. It is remarkable that in the reaction of 6a with 1a only endo-7 is formed. With silicagel in ether endo-7 isomerizes to the thermodynamically more stable exo-7 (Schemes 3 and 6). The crystal structure of the latter compound has been established by X-ray crystallography. The reaction of 6a and 2-isopropyl-3-phenyl- cyclopropenone (1b) yields only one product, which isomerizes with silicagel in ether to exo-10 (Scheme 4). The structure of exo-10 has been determined by NMR- spectroscopy. It seems reasonable that this structure results from a nucleophilic attack of the four-membered amidine to the phenyl-substituted C-atom of 1b.

Naturally Occurring Cyclopropenone Derivatives

Naturally Occurring Cyclopropenone Derivatives

Structure and reactivity of cyclopropenones and triafulvenes.

Structure and reactivity of cyclopropenones and triafulvenes.

Additions and Corrections - The Isolation and Characterization of Pure Cyclopropenone

Additions and Corrections - The Isolation and Characterization of Pure Cyclopropenone

The infrared spectrum of dichlorocyclopropenone

Abstract Dichloro cyclo propenone provides an opportunity to study a three-membered ring molecule with double bonds internal and external to the ring. It belongs to the symmetry group C 2 v , and possesses 12 fundamental vibrations (5 a 1 + 1 a 2 + 2 b 1 + 4 b 2 ). The infrared vapor, solution and solid phase spectra have been obtained and eight of the infrared active fundamentals are assigned.

Some observations on the infrared spectra of cyclopropenones

Some observations on the infrared spectra of cyclopropenones