Thiosuccinimide-linked antibody-drug conjugates (ADCs) are susceptible to drug loss over time due to a retro-Michael reaction, which can be prevented by selecting stable conjugation positions or hydrolysis of the thiosuccinimide. Here, we investigate pyrrolobenzodiazepine (PBD) ADC drug-linkers equipped with N-phenyl maleimide functionality for stable thiol conjugation via thiosuccinimide hydro...

Abstract Dual functionalization of targeting vectors, such as peptides and antibodies, is still synthetically challenging despite the increasing demand for molecules serving multiple purposes (i.e., optical nuclear imaging). Our strategy was to synthesize a versatile building block via orthogonal incorporation chemical entities (e.g., radionuclide chelator, fluorescent dye, cytotoxic drugs, cli...

Various indolylmaleimides (IMs) were synthesized, and their fluorescence (FL) and chemiluminescence (CL) were measured. The substitution at the 2-position of the indole ring and the 3- or 4-position of the maleimide moiety caused an obvious change in the FL and CL of the IMs. An almost on-off switching of the FL of the IMs was observed. The intramolecular charge transfer from the indole moiety ...

Molecular structures such as conformation and orientation are crucial in determining the activity of peptides immobilized to solid supports. In this study, sum frequency generation (SFG) vibrational spectroscopy was applied to investigate such structures of peptides immobilized on self-assembled monolayers (SAMs). Here cysteine-modified antimicrobial peptide cecropin P1 (CP1) was chemically imm...

The present study shows that the sulfur of the phosphorothioate 5'-nucleoside diphosphate beta-S adds across the olefinic double bond of the maleimide moiety of the thiol-sensitive probe, N-l pyrene maleimide. The reaction of phosphorothioate with the maleimide moiety provided a basis for coupling the phosphorothioate nucleoside diphosphate beta-S to maleimidederivatized bovine serum albumin. F...

In the present paper we describe the results of a preliminary study of the paramagnetic resonance spectrum of spin-labeled horse hemoglobin in solution. Our results provide strong evidence that on oxygenation the A chains undergo a significant structural change near the "reactive" sulfhydryl group (f693), a change not yet resolved by X-ray diffraction.' We also find features in the paramagnetic...

The one-pot [3 + 2] cycloaddition of an azomethine ylide with a maleimide followed by another [3 + 2] cycloaddition of an azide with the second maleimide gives a 1,5-diamino intermediate which is used for a sequential aminomethylation reaction with formaldehyde through [5 + 1] annulation to afford a novel polycyclic scaffold bearing tetrahydroquinazoline, pyrrolidine, pyrrolidinedione, and N-su...

Many protein kinase (PK) inhibitors have been reported in recent years, but only a few have been approved for clinical use. The understanding of the available molecular information using computational tools is an alternative to contribute to this process. With this in mind, we studied the binding modes of 77 maleimide derivates inside the PK glycogen synthase kinase 3 beta (GSK3β) using docking...

A robust, nanoelectromechanical switch is proposed based upon an asymmetric pendant moiety anchored to an organic backbone between two C60 fullerenes, which in turn are connected to gold electrodes. Ab initio density functional calculations are used to demonstrate that an electric field induces rotation of the pendant group, leading to a nonlinear current-voltage relation. The nonlinearity is s...

The Ca2(+)-ATPase in native sarcoplasmic reticulum membranes was selectively spin-labeled for saturation transfer electron spin resonance (ESR) studies by prelabeling with N-ethylmaleimide and by using low label/protein ratios. Results with the nitroxide derivative of the standard sulphydryl-modifying reagent, maleimide, were compared with a series of six novel nitroxide beta-substituted vinyl ...