Selective Peptide Cysteine Manipulation on Demand and Difficult Protein Chemical Synthesis Enabled by Controllable Acidolysis of N,S-Benzylidene Thioacetals

Although solid-phase peptide synthesis combining with chemical ligation provides a way to build up customized polypeptides in general, many targets are still presenting challenges for the conventional synthetic process, such as hydrophobic proteins. New methods and strategies are still required to overcome these obstacles. In this study, kinetic studies of Cys/Pen ligation and its acidolysis were performed, from which the fast acidolysis of substituted N,S-benzylidene thioacetals (NBTs) was discovered. The study demonstrates the potential of NBTs as a promising Cys switchable protection, facilitating the chemical synthesis of peptides and proteins by efficiently disrupting peptide aggregation. The compatibility of NBTs with other commonly adopted Cys protecting groups and their applications in sequential disulfide bond formation were also investigated. The first chemical synthesis of the native human programmed death ligand 1 immunoglobulin V-like (PD-L1 IgV) domain was achieved using the NBT strategy, showcasing its potential in difficult protein synthesis.     

ATP Synthesis by Rotary Catalysis (Nobel lecture)

The cyclic modulation of nucleotide-binding properties of the three catalytic β subunits by a series of conformational changes was an attractive explanation for the postulated binding change mechanism of ATP synthase. In the crystal structure of the catalytic F₁ domain of this enzyme there is indeed a complex made up of three α subunits and three β subunits arranged in alternation around a central α-helical segment of the γ subunit. This complex is asymmetric owing to the different conformations of the β subunits. The change in conformation is brought about by rotation of the rigid yet curved segment, which has meanwhile been proven experimentally.     

The Crystal Structure of a Potassium Channel— A New Era in the Chemistry of Biological Signaling

The similarity to crown ethers is apparent when the arrangement of the oxygen atoms of the carbonyl groups of the protein backbone in the structure of the potassium channel (see schematic drawing of a section of the structure) found in the bacterium Streptomyces lividans is considered. This particular part of the channel pore acts as the selectivity filter, with the permeability of the channel for K⁺ being as much as 10 000 times greater than for the Na⁺ ion. In fact, in this area of the structure two K⁺ ions are located, a feature that enables high flux through the channel.     

Cooperative Hydrogen Bonding and Enzyme Catalysis

An important contribution to enzyme catalysis may be made by cooperative effects—which are induced by the interactions of a negatively charged ligand L with peptide hydrogen bond networks—through stabilization of charge formation along the reaction pathway. This has been found from density functional calculations on model systems for peptide hydrogen bond networks (an example is shown in the picture).     

Layer-by-Layer self-assembly of polyaspartate and Poly(ethyleneimine) on magnetic nanoparticles: Characterization and adsorption of protein

Magnetic nanoparticles (MNPs) were modified by polyaspartate (PAA) and poly(ethyleneimine) (PEI) via Layer-by-Layer self-assembly. Two steps were involved in: the first was to coat MNPs by PAA at pH = 6; the second was to coat the former by PEI. The successful surface modification of MNPs was confirmed using X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA) and fourier transform infrared (FTIR) measurements. The modified MNPs interact strongly with negative fibrinogen and weakly with neutral γ-globin and positive lysozyme.     

A concise synthesis of meridianin F

A concise synthesis of the protein kinase inhibitor meridianin F has been achieved in good overall yield starting from 5,6-dibromoindole-3-carbaldehyde.     

Facile synthesis of N-6 adenosine modified analogue toward S-adenosyl methionine derived probe for protein arginine methyltransferases

Chemically modified cellular co-factors that provide function,such as immobilization or incorporation of fluorescent dyes,are valuable probes of biological activity.A convenient route to obtain S-adenosyl methionine(AdoMet) analogues modified at N-6 adenosine to feature a linker terminating in azide functionality is described herein.Subsequent decoration of such AdoMet analogues with guanidinium terminated linkers leads to novel potential bisubstrate inhibitors for protein arginine methyltrans-ferases, PRMTs.