Enediyne-based protein capture agents: demonstration of an enediyne moiety acting as a photoaffinity label

Abstract

Two enediyne based protein-capture compounds 1 and 2 were synthesized. Both these molecules have an aryl sulfonamide for reversible binding with Human Carbonic Anhydrase II (HCA II) and a pyrene moiety for the visualization of a capture event. While compound 1 has an aryl azide as a photo cross-linking agent, compound 2 lacks the azide moiety. Capture experiments with HCA II however show that both 1 and 2 can photo cross-link with the protein as indicated in gel electrophoresis as well as MALDI analysis after tryptic digestion of HCA II. This observation demonstrates the ability of the enediyne moiety to act as a photo-affinity label possibly via the addition of nucleophilic amino acids to the partially zwitterionic singlet form of the diradical generated by photo Bergman cyclization.

Triggering the Antitumor Activity of Acyclic Enediyne through Maleimide-Assisted Rearrangement and Cycloaromatization

“…To clarify the unique role of maleimide moiety in the cyclization of enediynes, two model compounds equipped with the same alkyne functionalities were designed. EDY-A features a benzene group at the ene position, representing common acyclic enediynes, − while EDY-B features a maleimide group at the same position. The two tert -butyl groups of different types were installed in the terminal alkyne, tert -butyl tert -butyl­(prop-2-yn-1-yl)­carbamate ( 1 ), as chemical shift indicators for nuclear magnetic resonance (NMR) analysis.…”

Naphthalimide-Based Template for Inhibitor Screening via Cross-Linking and In-Gel Fluorescence: A Case Study against HCA II

“…All biochemical experiments have been done as described in our previous papers. 18,17 Preparation of GABA-Carboxylic Acid (14). The procedure for preparation of the GABA-carboxylic acid derivative is same as that reported earlier.…”

“…The following abbreviations have been used for NMR peak assignments: s = singlet, bs = broad singlet, d = doublet, t = triplet, p = pentet, m = multiplet, and dd = double of doublet. All biochemical experiments have been done as described in our previous papers. , …”

Enediyne-Comprising Amino Aldehydes in the Passerini Reaction

“…The remarkable activity and a striking mode of action made enediyne compounds an attractive target molecules. Motivated by their biological importance, many cyclic and acyclic enediyne derivatives were prepared and their biological activities evaluated. − Apart from their role in biologically relevant processes, enediynes are versatile building blocks for the construction of complex aromatic systems through thermal or photochemical activation. − Furthermore, rigid, stable, and spatially well-directed enediyne motif can be exploited as an inducer of turn-like conformation. In our previous studies, we showed that enediyne-based small molecule tweezers are efficient Cu­(II) atom binders .…”