Israel Journal of Chemistry最新文献

Conflict of interest

No conflicts to declare.

Genetically encoded peptide libraries are at the forefront of de novo drug discovery. The RaPID (Random Nonstandard Peptides Integrated Discovery) platform stands out due to the unique combination of flexible in vitro translation (FIT) and mRNA display. This enables the incorporation of non-canonical amino acids, improving chemical diversity and allowing macrocyclisation of the peptide library. The resulting constrained peptides are valued for their strong binding affinity and stability, especially in the context of protein-protein interactions. In response to SARS-CoV-2, the causative agent of the COVID-19 pandemic, the RaPID system proved valuable in identifying high-affinity ligands of viral proteins. Among many peptide ligands of SARS-CoV-2 spike and main protease (M^pro), several macrocycles stand out for their exceptional binding affinities. Structural data showcases distinct binding modes in complex with the receptor-binding domain (RBD) of the spike glycoprotein or the catalytic active site of M^pro. However, translating these in vitro findings into clinical applications remains challenging, especially due to insufficient cell permeability.

Surface characterization is essential for understanding chemical and electrochemical transformations occurring on surfaces or at interfaces. Battery electrode aging processes, biofilm growth, crystallization, and transport/signaling across cellular membranes are only a few examples of such phenomena. This special issue delves into applied electrochemistry and nonlinear optical techniques applicable to surface characterization.

Near-field techniques usually require specialized instrumentation. However, although much improvement has been made over recent years, many surface-characterization tools are still limited to samples in a vacuum; therefore, in-situ and in-operando experiments are impractical. On the other hand, optical techniques are more flexible and less demanding regarding sample handling. Still, they usually need more surface specificity and sensitivity, and in principle, they have a lower resolution compared to electron beam-based techniques.

On the other hand, optical techniques also offer different contrast modalities. For example, Second-harmonic generation (SHG) or surface-enhanced Raman spectroscopy (SERS) are versatile optical tools for probing surfaces. From symmetry considerations, SHG responses are forbidden from the bulk of metallic electrodes and observed only from the surface where the symmetry is broken. Thus, high sensitivity can be attained using SHG, and when both SHG and SERS are combined, selectivity and sensitivity can be achieved. In addition, nanofabrication of metallic surfaces can further improve the sensitivity of SHG and SERS by orders of magnitude due to local field enhancement.

In recent years, much improvement has been made in super-resolution microscopy and imaging, enabling fast yet high-resolution imaging over areas as large as half-by-half-millimeter squares. For the field of electrochemistry, such development is very important since it may open the door for real-time optical characterization of solid-liquid interfaces during charging/discharging cycles, which can potentially lead to significant improvements in the performance and durability of the electrode. These contributions not only expand the horizons of applied electrochemical science but also underline its influence on our daily lives and its pivotal role in addressing global challenges related to climate and energy.

Cucurbiturils are popular macrocyclic receptors that bind complementary guest molecules with high affinity in aqueous environments. They are recognized for their ability to selectively bind positively charged guest molecules, including ionizable ammonium cations which frequently display much higher affinity than their neutral counterparts. This selectivity for the protonated species is translated into an increase in the basicity of encapsulated guests (i. e. into complexation-induced positive pK_a shifts). However, despite being very rare, negative pK_a shifts can be observed for specific guests. Following a previous work from our group reporting slightly negative pK_a shifts for flavylium and chalcone dyes featuring N-diethylamino substituents (ΔpK_a=− 0.2), herein we report a systematic study on the complexation of N-dialkylaminochalcones with CB7. The results show that the pK_a shifts of these host-guest complexes can be rationally tuned by the nature of the N-dialkylamino groups and as well by target substitutions on the skeleton of the dye, allowing the design of a CB7 1 : 1 host-guest complex with a ΔpK_a=− 0.6.

This special issue commemorates the life and work of Prof. Richard A. Lerner. Prof. Lerner's mix of creativity, fearlessness, and unboundedness conceived and conceptualized inventions like catalytic antibodies, antibody libraries, and DNA-encoded small molecule libraries.