On December 12th, 2023, the European Commission took regulatory action to amend Annex XVII of REACH, imposing restrictions on the use of N,N‐dimethylformamide (DMF) within the EU market owing to its high toxicity. Historically, DMF has been widely considered the gold standard for solid‐phase peptide synthesis (SPPS). Being urgent to propose alternative solvents, we tested the suitability of non‐hazardous neat and mixed solvents. Notably, binary solvent mixtures containing dimethyl sulfoxide as one of the solvent partners demonstrated high efficacy in solubilizing reagents while maintaining the desired swelling characteristics of common resins. A series of binary solvent mixtures were tested in automated SPPS, both at room temperature and high temperature, employing the PurePep® Chorus synthesizer, which enabled controlled induction heating between 25 and 90°C with oscillation mixing. The performances were assessed in challenging peptide sequences, i.e., ACP (65–74), and in longer and aggregating sequences like SARS‐CoV‐2 RBM (436–507) and β‐amyloid (1–42). Furthermore, as part of the proposed sustainable approach to minimize the utilization of hazardous solvents, we coupled the novel PurePep EasyClean catch‐and‐release purification technology. This work, addressing regulatory compliance, emphasizes the crucial role of green chemistry in advancing safer and more environmentally friendly practices in SPPS.

This study illustrates the sensing and wound healing properties of silk fibroin in combination with peptide patterns, with an emphasis on the printability of multilayered grids, and envisions possible applications of these next-generation silk-based materials. Functionalized silk fibers covalently linked to an arginine–glycine–aspartic acid (RGD) peptide create a platform for preparing a biomaterial ink for 3D printing of grid-like piezoresistors with wound-healing and sensing properties. The culture medium obtained from 3D-printed silk fibroin enriched with RGD peptide improves cell adhesion, accelerating skin repair. Specifically, RGD peptide-modified silk fibroin demonstrated biocompatibility, enhanced cell adhesion, and higher wound closure rates at lower concentration than the neat peptide. It was also shown that the printing of peptide-modified silk fibroin produces a piezoresistive transducer that is the active component of a sensor based on a Schottky diode harmonic transponder encoding information about pressure. We discovered that such biomaterial ink printed in a multilayered grid can be used as a humidity sensor. Furthermore, humidity activates a transition between low and high conductivity states in this medium that is retained unless a negative voltage is applied, paving the way for utilization in non-volatile organic memory devices. Globally, these results pave the way for promising applications, such as monitoring parameters such as human wound care and being integrated in bio-implantable processors.

Numerous RNA‐binding proteins have modular structures with folded domains and intrinsically disordered regions, making their atomic characterization difficult. This severely limits the investigation of their modalities of interaction as well as the evaluation of possible ways to interfere with this process. We report herein a rational strategy for the design and synthesis of a ligand able to interfere with the protein function, monitoring the interaction through solution nuclear magnetic resonance spectroscopy. Our approach employs a chimaera composed of two different fragments, a peptide and a peptide‐nucleic acid, allowing to incorporate in the resulting molecule key features to address RNA‐protein interactions. Focusing on two constructs of the Nucleocapsid protein from SARS‐CoV‐2, the globular N‐terminal domain and a more extended one comprising also two flanking intrinsically disordered regions, we demonstrate the enhanced affinity of the designed peptide‐peptide nucleic acid chimaera for the protein compared to a related peptide lacking π–π stacking contributions within the chain. Furthermore, we emphasize the increasingly recognized relevant and synergistic role of the intrinsically disordered regions in protein‐ligand interaction.

Bicyclic peptides are a promising class of compounds. Compared to monocyclic molecules, they have advantages, e.g. increased stability or membrane permeability, or higher selectivity possibly. Owing to their abilities they are a promising class of ligands for metal ions.

The combination of pharmacologic and endoscopic therapies is the gold standard for treating intestinal failures. The possibility of chemical solubility in water is mandatory for intelligent capsules. Functionalised silk fibroin with peptides and covalently linking different molecular entities to its structure make this protein a platform for preparing gels dissolving in the small and large intestine for drug delivery. In the present study, we linked a peptide containing the cell-adhesive motif Arginine–Glycine–Aspartic acid (RGD) to degummed silk fibres (DSF). Regenerated silk fibroin (RS) films obtained by dissolving functionalised DSF in formic acid were used to prepare composite gelatin. We show that such composite gelatin remains stable and elastic in the simulated gastric fluid (SGF) but can dissolve in the small and large intestines’ neutral-pH simulated intestine fluid (SIF). These findings open up the possibility of designing microfabricated and physically programmable scaffolds that locally promote tissue regeneration, thanks to bio-enabled materials based on functionalised regenerated silk.

Objective: Rheumatoid arthritis (RA) associated interstitial lung disease (ILD) is the most common pulmonary manifestations of RA, with a progressive course and a poor survival. An early detection and better treatment is essential to improve outcome. We evaluated 16 analytes that could be relevant for the development of RA ILD. Method: In an inception cohort of 1118 early RA patients, pulmonary fibrosis (PF) were identified in 60 patients after a mean follow-up of 5.3 years using high resolution computer tomography (HRCT). As controls, 124 early RA patients without PF and 94 matched population controls without known rheumatic disease were studied. Analysis of antibodies against histones 3 and 4 derived citrullinated peptides (CitH3/H4), and cytokines/chemokines levels were performed in plasma samples collected at RA diagnosis using in-house ELISA and Luminex analysis. Result: Anti-CitH3(114–135) antibodies were the only antibody with increased frequency and levels in patients with PF versus without PF. The highest OR for PF development were found when combining positivity for anti-CitH3(114–135) and -CitH4(31–50) antibodies, OR 2.26. Levels of IL1α, IL1ß, TNFα, VEGFA and MIPα remained significantly elevated in patients with PF compared without PF, after adjustments and Bonferroni corrections. Several of the cytokines/chemokines correlated significantly with the histone antibodies in patients without PF. Partial least squares discriminant analysis including antibodies against citrullinated histon peptides and cytokines/chemokines identified significantly in PF in non-smokers. Conclusion: Antibodies against CitH3 peptides and several of the analysed cytokines/chemokines in samples collected at diagnosis were associated with subsequent delevopment of PF in patients with RA.