Search Results (140)

This review examines the feasibility of electrochemical synthesis of poly-L-arginine (PArg) using repetitive cyclic voltammetry in neutral aqueous phosphate-buffered saline. Previous studies on electrochemical deposition of PArg onto different carbonaceous electrode materials are discussed with respect to the already reported mechanistic models. Some controversial interpretations are of interest, predominantly the formation of peptide bonds during the electropolymerisation of L-arginine. Several alternative anodic pathways are considered via the possibilities and limitations of ways of attaching L-arginine molecules to the electrode surface. Furthermore, the role of oxygen-containing surface groups is discussed, as this aspect has been largely overlooked in the context of L-arginine deposition, despite the O-terminating character of the electrode surface and its effect on the reactivity of the nucleophilic guanidine group in L-arginine. Also, the application of extremely high potentials around +2 V vs. Ag/AgCl/3 mol L⁻¹ KCl is considered, as it can lead to the generation of reactive oxygen species that may interfere with or even govern the entire deposition process. Thus, the absence of such considerations may raise doubts about the peptide nature of the electrochemically assisted polymerisation of this basic amino acid. Finally, it seems that the identity of the electrochemically synthesised PArg does not correspond to that of this polymer prepared by conventional methods, such as solid-phase peptide synthesis, solution-phase synthesis, or N-carboxy-anhydride polymerisation, and therefore the whole process remains unproved. Full article

Nucleopeptides (NPs) are unnatural hybrid polymers designed by coupling nucleobases to the side chains of amino acid residues within peptides. In this study, we present the synthesis of an Fmoc-protected nucleobase amino acid (NBA) monomer (Fmoc-1,4-TzlNBA_A) with adenine attached to the side chain of L-homoazidoalanine (Aha) through a 1,4-linked-1,2,3-triazole. The coupling was accomplished by a Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) of Fmoc-Aha and N9-propargyladenine. Subsequently, a homotrinucleopeptide (HalTzl_AAA) containing three 1,4-TzlNBA_A residues was synthesized, using different solid-phase peptide synthesis (SPPS) approaches, and its ability to recognize U-rich motifs of RNAs involved in the HIV replication cycle was studied using circular dichroism (CD) and fluorescence spectroscopy. CD curves confirmed the binding of HalTzl_AAA to U-rich motifs of the transactivation responsive element (TAR UUU RNA HIV-1) bulge and the anticodon stem–loop domain of human tRNALys3 (ASLLys3) by a decrease in the positive ellipticity band intensity around 265 nm during the complexation. 5′-(FAM(6))-labeled TAR UUU and hASLLys3 were used for fluorescence anisotropy binding studies. Fluorescence data revealed that HalTzl_AAA bound TAR’s UUU bulge with a moderate affinity (K_d ≈ 38 µM), whereas the ASLLys3 UUUU-containing loop sequence was recognized with 2.5 times lower affinity (with K_d ≈ 75 µM). Both the standard SPPS method and its variants, which involved the attachment of adenine to the L-Aha side chain using the click reaction during the synthesis on the resin or after the nucleopeptide cleavage, were characterized by a similar efficiency and yield. The CD and fluorescence results demonstrated that HalTzl_AAA recognized the U-rich sequences of the RNAs with moderate and varied affinities. It is likely that both the hydrogen bonds associated with the complementarity of the interacting sequences and the conformational aspects associated with the high conformational dynamics of U-rich motifs are important in the recognition process. The nucleopeptide represents a new class of RNA binders and may be a promising scaffold for the development of new antiviral drugs. Full article

Hydrogen atom transfer (HAT) is a fundamental class of radical transformations that enables the direct generation of open-shell radical intermediates from R–H bonds (R = C, N, etc.), offering unique opportunities for green and sustainable synthesis. Significant progress has been made not only in identifying diverse molecular scaffolds capable of mediating HAT but also in developing synthetic methodologies to achieve precise stereocontrol in these processes. In this context, this review highlights recent advances in the use of sugar-derived compounds, cysteine-containing peptides, and chiral/achiral thiols/thiophenols as catalysts for stereoselective HAT, emphasizing their potential to expand the synthetic utility of HAT in organic transformations. Full article

In this work, a novel solid polymer electrolyte with a disordered structure has been designed, combining polyethylene glycol (PEG) as the flexible segments and hexamethylene diisocyanate (HDI) as the rigid segments. The synthesis was realized by alternating flexible PEG with rigid HDI through a peptide bond (–CO–NH–), which disrupts the ordered structures of PEG, generating electron-deficient Lewis acid groups. The pathbreaking introduction of HDI blocks not only bridges links between the PEG molecules but also generates electron-deficient Lewis acid groups. Therefore, the original ordered structures of PEG are disrupted by both the alternating chains between PEG and HDI and the Lewis acid groups. As a result, the PEG_H/L4000 electrolytes (PEG molecular weight of 4000) exhibit a strong anion-capture ability that decreases the crystallinity of polymers, which further achieves a high ionic conductivity close to 10⁻³ S·cm⁻¹ with the lithium-ion transference numbers up to 0.88. The symmetric Li|PEG_H/L4000|Li cells maintain a low and stable voltage polarization for more than 800 h at 0.1 mA·cm⁻². Furthermore, the LiFePO₄|PEG_H/L4000|Li all-solid-state cells perform well both in cycling and rate performances. The design of polymer disordered structures for polymer electrolytes provides a new thought for manufacturing all-solid-state lithium-ion batteries with high safety as well as long life. Full article

Background/Objectives: Peptide-based inorganic nanoparticles (PINPs) have emerged as promising candidates for intracellular delivery due to their unique structural and functional attributes. These hybrid nanostructures combine the high surface area and tunable optical/magnetic properties of metal cores (e.g., Au, Ag, Fe₃O₄) with the biocompatibility, targeting specificity, and responsive behavior of peptides. In particular, peptides with amphipathic or cell-penetrating features could facilitate efficient transport of molecular cargos across cellular membranes while enabling stimulus-responsive drug release in target tissues. Methods: We review key synthesis methods (especially green, peptide-mediated one-pot approaches), functionalization strategies (e.g., thiol-gold bonds, click chemistries), and characterization techniques (TEM, DLS, FTIR, etc.) that underpin PINP design. In addition, we highlight diverse peptide classes (linear, cyclic, amphipathic, self-assembling) and their roles (targeting ligands, capping/stabilizing agents, reducing agents) in constructing multifunctional nanocarriers. Results: The prospects of PINPs are considerable: they enable targeted drug delivery with imaging/theranostic capability, improve drug stability and cellular uptake, and harness peptide programmability for precision nanomedicine. However, challenges such as in vivo stability, immunogenicity, and standardization of evaluation must be addressed. Conclusions: Overall, PINPs represent multifunctional platforms that could significantly advance drug delivery and diagnostic applications in the future. Full article

Background/Objectives: PEGylated liposomes are widely recognized for their biocompatibility and capacity to extend systemic circulation via “stealth” properties. However, the PEG corona often limits tumor penetration and cellular internalization. Targeting matrix metalloproteinase-2 (MMP-2), frequently upregulated in breast cancer stroma, presents an opportunity to enhance tissue-specific drug delivery. In this study, we engineered MMP-2-responsive GPLGVRG peptide-modified cleavable PEGylated liposomes for targeted paclitaxel (PTX) delivery. Methods: Molecular docking simulations employed the MMP-2 crystal structure (PDB ID: 7XJO) to assess GPLGVRG peptide binding affinity. A cleavable, enzyme-sensitive peptide-PEG conjugate (Chol-PEG_2K-GPLGVRG-PEG_5K) was synthesized via small-molecule liquid-phase synthesis and characterized by ¹H NMR and MALDI-TOF MS. Liposomes incorporating this conjugate (S-Peps-PEG_5K) were formulated to evaluate whether MMP-2-mediated peptide degradation triggers detachment of long-chain PEG moieties, thereby enhancing internalization by 4T1 breast cancer cells. Additionally, the effects of tumor microenvironmental pH (~6.5) and MMP-2 concentration on drug release dynamics were investigated. Results: Molecular docking revealed robust GPLGVRG-MMP-2 interactions, yielding a binding energy of −7.1 kcal/mol. The peptide formed hydrogen bonds with MMP-2 residues Tyr A:23 and Arg A:53 (bond lengths: 2.4–2.5 Å) and engaged in hydrophobic contacts, confirming MMP-2 as the primary recognition site. Formulations containing 5 mol% Chol-PEG_2K-GPLGVRG-PEG_5K combined with 0.15 µg/mL MMP-2 (S-Peps-PEG_5K +MMP) exhibited superior internalization efficiency and significantly reduced clonogenic survival compared to controls. Notably, acidic pH (~6.5) induced MMP-2-mediated cleavage of the GPLGVRG peptide, accelerating S-Peps-PEG_5K dissociation and facilitating drug release. Conclusions: MMP-2-responsive, cleavable PEGylated liposomes markedly improve PTX accumulation and controlled release at tumor sites by dynamically modulating their stealth properties, offering a promising strategy to enhance chemotherapy efficacy in breast cancer. Full article

The title compound, 4-(4-formyl-3,5-dimethoxyphenoxy)butyric acid (BAL), is an important “handle” for solid-phase synthesis of peptides and related compounds. Reported here is an X-ray single crystal structural analysis of BAL. The molecule is almost entirely flat, and the crystal is held together by π-stacking and hydrogen bonding. Full article

Peptides are molecules composed of two or more amino acids linked by peptide bonds, and they play essential biological roles. In recent decades, peptides have become pivotal bioactive ingredients in pharmaceuticals and cosmetics due to their unique features. Originally developed for therapeutic purposes, peptides have gained popularity in the cosmetic field, providing solutions for anti-aging, whitening, moisturizing, and skin repair. Moreover, innovations such as artificial intelligence-assisted peptide design, efficient delivery systems, and the integration of multifunctional ingredients have significantly contributed to the industry’s rapid evolution. This review explores the historical milestones of peptides in medicine and cosmetics, delves into cutting-edge synthesis technologies, and dissects the molecular mechanisms behind their cosmetic properties. Research in medicinal peptides has promoted the development of cosmetic peptides. Despite their potential, challenges such as stability, bioavailability, and cost-effective production remain barriers to widespread adoption. Future studies should focus on enhancing peptide stability, developing synergistic formulations, and conducting large-scale clinical trials to validate long-term efficacy. With continuous innovation, peptides are poised to redefine the cosmetic industry, bridging the gap between pharmaceuticals and skincare for safer and more effective solutions. Full article

This study investigated the structure–activity relationships between SePEPs (selenium-enriched peptides) and PEPs (selenium-free peptides) and compared the antioxidant activities of SePEPs and PEPs. The results showed that SePEPs exhibited higher antioxidant activity than PEPs at the same molecular weight, with the molecular weights of 0–3500 Da exhibiting the highest in vitro antioxidant activity. Chelation between selenium and peptides led to a more compact structure and increased particle density in SePEPs. A spectroscopic analysis revealed new peaks and redshifts in SePEPs, along with a higher content of hydrophobic amino acids than PEPs. A molecular interaction modeling analysis indicated that hydrogen bonding and hydrophobic interactions primarily drove the binding between selenium-containing peptides and 1,1-diphenyl-2-picrylhydrazyl (DPPH). Moreover, the solid-phase synthesized MSePGP exhibited significantly greater antioxidant activity than glutathione at high concentrations. At 10 mg/mL, the DPPH radical scavenging rate of MSePGP was 68.5 ± 2.2%. These findings provide a theoretical basis for the design and synthesis of selenium-enriched peptides with enhanced antioxidant properties. Full article

Proteins are structurally and functionally diverse biomacromolecules that serve a variety of essential activities to ensure complex biological homeostasis. The desire to elucidate and enhance these biological functions has been at the forefront of research for many decades. However, generating active proteins via recombinant expression or through chemical total synthesis each has limitations in terms of yield and functionality. Nature has provided a solution to this problem through evolving protein ligases that catalyze the formation of amide bonds between peptides/proteins, which can be exploited by protein engineers to develop robust functional proteins. Here, we summarize the biochemical mechanisms and applications of multiple cysteine-based protein ligases, especially focusing on how they have been utilized for protein therapeutics and engineering, as well as how they inspired chemists to develop efficient methodologies for protein synthesis (e.g., native chemical ligation). Full article

Disulfide bonds are crucial for stabilizing bioactive peptides such as conotoxins. We have developed a method for synthesizing conotoxins with three disulfide bonds using Mob, Trt, and Acm protection groups for regionally selective synthesis. This approach enabled the efficient synthesis of peptides with the desired disulfide bond connectivities independent of their sequences. Using our strategy, we synthesized five conotoxins, achieving yields of 20–30%. The results demonstrate the potential of our method for synthesizing complex peptides with multiple disulfide bonds. Full article

Acetamidomethyl (Acm)-protected cysteine derivatives are essential components of multi-disulfide synthesis, particularly due to the availability of multimodal removal conditions for Acm protection. Most of these removal conditions are harsh and are commonly used to remove Acm protection at the last step of regioselective synthesis of a multi-disulfide, implying that the removal of Acm is performed in the absence of other Cys thiol protections. In this context, N-chlorosuccinimide (NCS)-mediated removal of Acm and concomitant disulfide bridge formation provides a fast and reliable way to synthesize multi-disulfides. In the present study, we demonstrate that NCS-mediated Acm removal and disulfide bond formation can be performed in the presence of other commonly used Cys thiol protections. Interestingly, Acm can be removed with NCS without affecting the Trt group, which is also removed with I₂. Later, we successfully employ the NCS-based Acm removal method in the synthesis of multi-disulfide peptides like α-conotoxin SI. Full article

Conotoxins are a class of peptide toxins secreted by marine mollusks of the Conus genus, characterized by their unique mechanism of action and significant biological activity, making them highly valuable for drug development. However, traditional methods of acquiring conotoxins, such as in vivo extraction or chemical synthesis, face challenges of high costs, long cycles, and limited exploration of sequence diversity. To address these issues, we propose the ConoGPT model, a conotoxin sequence generation model that fine-tunes the ProtGPT2 model by incorporating disulfide bond information. Experimental results demonstrate that sequences generated by ConoGPT exhibit high consistency with authentic conotoxins in physicochemical properties and show considerable potential for generating novel conotoxins. Furthermore, compared to models without disulfide bond information, ConoGPT outperforms in terms of generating sequences with ordered structures. The majority of the filtered sequences were shown to possess significant binding affinities to nicotinic acetylcholine receptor (nAChR) targets based on molecular docking. Molecular dynamics simulations of the selected sequences further confirmed the dynamic stability of the generated sequences in complex with their respective targets. This study not only provides a new technological approach for conotoxin design but also offers a novel strategy for generating functional peptides. Full article

Royal jelly and medical grade honey are traditionally used in treating wounds and infections, although their effectiveness is often variable and insufficient. To overcome their limitations, we created novel amphiphiles by modifying the main reparative and antimicrobial components, queen bee acid (hda) and 10-hydroxyl-decanoic acid (hdaa), through peptide bonding with specific tripeptides. Our molecular design incorporated amphiphile targets as being biocompatible in wound healing, biodegradable, non-toxic, hydrogelable, prohealing, and antimicrobial. The amphiphilic molecules were designed in a hda(hdaa)-aa1-aa2-aa3 structural model with rational selection criteria for each moiety, prepared via Rink/Fmoc-tBu-based solid-phase peptide synthesis, and structurally verified by NMR and LC–MS/MS. We tested several amphiphiles among those containing moieties of hda or hdaa and isoleucine–leucine–aspartate (ILD-amidated) or IL-lysine (ILK-NH₂). These tests were conducted to evaluate their prohealing and antimicrobial hydrogel properties. Our observation of their hydrogelation and hydrogel-rheology showed that they can form hydrogels with stable elastic moduli and injectable shear-thinning properties, which are suitable for cell and tissue repair and regeneration. Our disc-diffusion assay demonstrated that hdaa-ILK-NH₂ markedly inhibited Staphylococcus aureus. Future research is needed to comprehensively evaluate the prohealing and antimicrobial properties of these novel molecules modified from hda and hdaa with tripeptides. Full article

Developing affordable, rapid, and accurate biosensors is essential for SARS-CoV-2 surveillance and early detection. We created a bio-inspired peptide, using the SAGAPEP AI platform, for COVID-19 salivary diagnostics via a portable electrochemical device coupled to Machine Learning algorithms. SAGAPEP enabled molecular docking simulations against the SARS-CoV-2 Spike protein’s RBD, leading to the synthesis of Bio-Inspired Artificial Intelligence Peptide 1 (BIAI1). Molecular docking was used to confirm interactions between BIAI1 and SARS-CoV-2, and BIAI1 was functionalized on rhodamine-modified electrodes. Cyclic voltammetry (CV) using a [Fe(CN)₆]^3−/4 solution detected virus levels in saliva samples with and without SARS-CoV-2. Support vector machine (SVM)-based machine learning analyzed electrochemical data, enhancing sensitivity and specificity. Molecular docking revealed stable hydrogen bonds and electrostatic interactions with RBD, showing an average affinity of −250 kcal/mol. Our biosensor achieved 100% sensitivity, 80% specificity, and 90% accuracy for 1.8 × 10⁴ focus-forming units in infected saliva. Validation with COVID-19-positive and -negative samples using a neural network showed 90% sensitivity, specificity, and accuracy. This BIAI1-based electrochemical biosensor, integrated with machine learning, demonstrates a promising non-invasive, portable solution for COVID-19 screening and detection in saliva. Full article