Conventional drug delivery systems often face challenges related to inadequate control over release and insufficient structural stability. Peptide-based hydrogels with adjustable self-assembly properties represent promising solutions to these challenges. Herein, a series of antioxidant peptides was designed and synthesized to fabricate self-assembled peptide hydrogels. Various aliphatic amino acids were introduced as flexible linkers between dityrosine (YY) and diphenylalanine (FF) motifs to tune peptide self-assembly. Among them, AcNH-Tyr-Tyr-Ala-Phe-Phe-CONH₂ (YYAFF) formed a stable hydrogel with a uniform dense 3D network within only 1 min. It showed excellent thermal stability, good biocompatibility, and sustained release. Various characterization methods revealed that the YYAFF peptide self-assembled through random coils and β-sheets. The primary intermolecular interactions arose from hydrogen bonds and π-π stacking. Within the tumor microenvironment, the hydrogel demonstrated the capacity to effectively encapsulate doxorubicin (DOX), achieving a maximum encapsulation efficiency of 92.13 ± 1.25% under optimal conditions. The total release rate was 69.30% within 48 h. Molecular dynamics and docking revealed 15 hydrogen bonds and 7 π-π interactions dominated YYAFF-DOX binding. This study demonstrates the key role of flexible linkers in regulating peptide self-assembly and provides a rapidly gelling, biocompatible antioxidant peptide hydrogel for efficient antitumor drug delivery.

An easy and highly-sensitive electrochemical sensor for chlorophenols (CPs) was constructed based on the nanocomposite films of electrochemically-reduced graphene oxide-cationic pillar[6]arene (ErGO-CP6) using onestep potentiostatic electrodeposition method. Compared to the ErGO film, the ErGO-CP6 composite film added favourable electron transfer access and gave a better electrocatalytic performance of CPs oxidation because of the ErGO-CP6 synergy. This study selected 2-chlorophenol (2-CP, a typical CPs compound) as a model representative organic pollutant. The oxidation peak current of 2-CP was linearly proportional to the 0.01-39.5 mu M concentration range at optimal conditions, with a 0.005 mu M limit detection. The approach proposed in this study could conveniently determine the level of total CPs.

The photoinduced generation of reactive oxygen species (ROS) has attracted increasing attention for applications in cancer therapy, antimicrobial sterilization, pollutant degradation, and organic synthesis. Yet, achieving efficient ROS production under mild and environmentally benign conditions remains challenging. Here, we report a tetraphenylethylene-derived amphiphile (TPEC) that self-assembles into square nanosheets in water, exhibiting strong light absorption and blue fluorescence emission. To further enhance ROS generation, cetyltrimethylammonium bromide (CTAB) was employed to regulate the assembly morphology, yielding cyan-emissive nanoparticles that function as an effective light-harvesting platform. Co-assembly with two energy acceptor dyes, Eosin Y (ESY) and sulforhodamine 101 (SR101), constructed a sequential energy-transfer light-harvesting system (LHS) that displayed tunable emission from green to orange and enabled stepwise amplification of ROS production. Such a sequential LHS thus offers an effective strategy for simultaneously achieving controllable emission color and enhanced ROS generation, providing a versatile basis for diverse photochemical applications.

Aimed to enhance stabilities and enable targeted delivery of bioactives (tea polyphenols, TP; /3-carotene, /3C) with diverse solubilities, in this study, encapsulating gels were developed using small peptides (AcTFFNH2, YAFAF) and sodium alginate. Gel properties and bioactive retention were characterized via rheological tests and scanning electron microscopy (SEM). Specific formulations included peptide hydrogels (THG, YHG), composite hydrogels (TSG, YSG), emulgels (TEG, YEG), and composite emulgels (TSE, YSE), exhibiting distinct loading capacities. Bioactives concentration significantly influenced encapsulation efficiency and gel strength, with TP@TSG demonstrating optimal encapsulation (91.07 f 0.03 % efficiency, 5410 f 178 Pa of gel strength) and /3C@YSE showing high performance (96.52 f 0.22 % efficiency, 4120 f 84 Pa of gel strength). Following 4-h incubation under physiologically relevant stresses (pH, temperature, metal ions), all gels maintained protective capabilities. The release behavior of encapsulating gels revealed an environment-dependent release process. The analysis of release kinetics using multiple mathematical models indicated that bioactives release was controlled by a mixed diffusion-dissolution/erosion mechanism, driven synergistically by polymer swelling and degradation.

Background: The overuse of traditional antimicrobial agents has accelerated the global spread of drug-resistant bacteria, posing a severe threat to global public health. Methods: In this work, a series of lipopeptides with varying fatty acid chain lengths were designed using the targeting antimicrobial peptide CL5 as the parental peptide. A variety of technical methods, including spectroscopic techniques, electron microscopy and computer simulation, were adopted to explore the self-assembly properties of the lipopeptides and their antimicrobial properties against Gram-positive and Gram-negative bacteria. Results: The results showed that lipopeptide self-assembly could be triggered by fatty acid chain modification with a carbon chain length exceeding 8 atoms, and hydrophobic interactions between fatty acid chains were the primary driving force for this process. The geometric mean of the minimum inhibitory concentrations of the lipopeptides exhibited an approximate "U"-shaped correlation with the length of the fatty acid chains. Among these lipopeptides, C8CL5-C12CL5 exhibited broad-spectrum and highly potent antimicrobial activity, with geometric means of 6.20, 5.16, and 8.00 μM against all tested bacteria, and selectivity index values of 12.26, 8.14, and 7.48, respectively. Furthermore, the lipopeptides exhibited high selectivity, rapid time-killing kinetics, as well as excellent thermal, pH and salt stability. Mechanistic studies revealed that the lipopeptides exerted antimicrobial effects through multiple pathways: disrupted bacterial cell membranes and caused the leakage of cellular contents, bound to bacterial genomic DNA, and promoted the production of reactive oxygen species. Conclusions: Collectively, lipopeptides modified with appropriate fatty acid chains exhibit broad-spectrum and highly effective antimicrobial activity, making them promising alternatives to traditional antibiotics for the treatment of bacterial infections.

Peptide-based supramolecular assemblies provide experimentally accessible model systems for probing structure-property relationships in soft molecular materials. Here, three short β-sheet-forming peptides with graded histidine substitution were designed as minimal supramolecular networks to systematically examine how sequence-level variation regulates supramolecular organization, viscoelastic response, and pH-modulated molecular transport in aqueous environments. All peptides spontaneously assembled into β-sheet-rich nanofibrous networks, as confirmed by spectroscopic and microscopic characterization, and exhibited stable viscoelastic behavior with pronounced reversible self-recovery. Using doxorubicin as a representative small-molecule probe, the assemblies displayed distinct pH-dependent transport regimes, and kinetic analysis based on the Korsmeyer-Peppas model revealed sequence- and pH-dependent differences in release behavior. Rather than focusing on detailed molecular-level mechanisms, this work emphasizes experimentally accessible correlations between supramolecular network structure, mechanical response, and transport behavior. These results highlight histidine-substituted β-sheet peptide assemblies as adaptable soft-matter model systems for investigating pH-regulated transport phenomena in supramolecular networks.

Self-assembled peptide hydrogels have emerged as a research frontier in biomedical engineering due to their exceptional water-retention capacity and spatiotemporal drug release kinetics. Researchers can fabricate biomaterials with customizable structures and tailored functionalities by precisely engineering peptide sequences, modulating molecular self-assembly pathways, orchestrating intermolecular interactions, and optimizing strategies for loading active pharmaceutical ingredients (APIs). These intelligent biomaterials demonstrate significant potential across diverse applications, including targeted drug delivery systems, new anti-cancer therapies, bioactive wound healing scaffolds, 3D cell culture matrices, and biosensing interfaces. This paper systematically reviews the latest breakthroughs in the rational design strategy, self-assembly mechanism, advanced characterization technology and artificial intelligence-assisted development of peptide hydrogels. The analysis of the structure-activity relationship between intermolecular interactions and macroscopic performance was performed. This review establishes a theoretical cognitive framework for a multi-scale self-assembly mechanism, providing theoretical guidance for developing a functional delivery system with precise drug loading characteristics and excellent biocompatibility and providing data support for their practical applications in clinical medicine.

In this study, peptides with antimicrobial activity and specific pH-response gel properties were designed and synthesized by introducing phenylalanine into transactivating transcriptor peptide TAT (YGRKKRRQRRR). In order to investigate the antibacterial mechanism, the interactions of TAT and its analogs with DNA were studied using multiple methods. Antimicrobial results indicated that a lower content of phenylalanine is associated with better antimicrobial effects. The synthesized peptides can form hydrogels and maintain their antimicrobial activity under high pH value condition. Rheological experiments revealed that an increase in phenylalanine enhances the gel-forming properties of peptides. Results of circular dichroism spectroscopy suggest that this may be due to an increase on alpha-helical structure with increasing of phenylalanine. TEM results clearly demonstrate the different structures of the peptide under different pH conditions. It forms fibers or network structures under high pH value instead of nanoparticles under low pH value. Drug release experiments showed that the peptide hydrogels had different release effects in different pH environments, demonstrating their potential application as drug carriers.

This study designed and synthesized amphipathic peptides(KF-series peptides) containing lysine K and phenylalanine F to investigate the effects of positive charges on both antibacterial efficacy and gelation performance. Experimental observations via SEM demonstrated that peptides are capable of disrupting the bacterial membrane. Spectroscopic analysis indicates that with the number of positive charges increases, the binding mode of KF-series peptides with DNA transitions from intercalative binding and electrostatic binding to groove binding coupled with electrostatic binding. Antimicrobial experiments demonstrated that the antibacterial efficacy of KF-series peptides progressively enhanced with increasing positive charge quantity, while exhibiting broad-spectrum antimicrobial activity against palmar bacteria. Further structural analysis on KF-1 and KF-2 peptides were demonstrated by inducing their self-assembly into hydrogels in high pH value. TEM results showed distinct microscopic morphologies of the KF-1 peptide under varying pH conditions. Rheological data indicated that KF-1 exhibited superior rheological performance. Although increasing positive charges enhanced the antimicrobial activity of the peptides, this improvement compromised the stability of the gel structure. Therefore, maintaining an appropriate ratio between basic amino acids and nonpolar amino acids is crucial for designing peptides with both antimicrobial capability and gelation capability. This study provides novel insights into the design of innovative dual-functional antimicrobial peptide hydrogels.

Sesaminol is a natural functional compound of sesame with low bioaccessibility due to its high crystallinity. Here, a peptide-based self-assembly microgel was constructed to encapsulate sesaminol, reducing its crystallinity and improving its bioaccessibility. In this contribution, the peptide AcNH-Leu-Tyr-Tyr-CONH2 (LYY) was shown to form a mesoporous three-dimensional (3D) microgel through microstructure characterization. Various characterization methods revealed that the LYY peptide self-assembled through β-folds and random coils, and the primary intermolecular interactions arose from hydrogen bonding and the π-π stacking effect. Subsequently, sesaminol was encapsulated within the microgel through co-assembly. The maximum encapsulation efficiency of sesaminol was 80.8 ± 0.9%, mainly in the form of nanoparticles encapsulated in microgel by morphology characterization. The XRD results indicated that sesaminol primarily existed in an amorphous state following encapsulation. The cumulative release indicated that sesaminol had a sustained release effect in the encapsulation system. Its bioaccessibility and antioxidant levels were increased. Molecular docking indicated that the main interactions between sesaminol and the self-assembled structure were hydrogen bonding and π-π interactions. Establishing sesaminol encapsulation provides valuable data and theoretical support for the research of sesaminol and the sesame processing industry.

The health risks associated with antibiotic resistance underscore the urgent need to develop novel antibiotic alternatives. Here, we constructed self-assembling antimicrobial peptide derivatives (AMPDs) with broadspectrum and efficient antimicrobial activity by modifying AMP Ce(1-8) with hydrophobic groups. The results showed that the longer length fatty acid chain (more than 10 carbon numbers) modifications could drive lipopeptide self-assembly, and the hydrophobic interactions between fatty acid chains were the main driving force for self-assembly. The geometric means of the minimum inhibitory concentrations of the designed lipopeptides showed an approximately "U-shaped" relationship with the carbon numbers of the fatty acid chains, and the activity of the aromatic group-modified AMPs increased with increasing hydrophobicity of the aromatic groups. Among these AMPDs, C12Ce, C14Ce and FmocCe exhibited potent antimicrobial activity, with 8-to 12-fold increase in average antimicrobial activity compared with Ce(1-8). In addition, they had high selectivity and good stability. Antimicrobial mechanistic studies indicated that the self-assembled AMPDs disassembed into monomers when interacting with bacterial membranes, and then their hydrophobic tails inserted into the bacterial membranes, thereby disrupting cell membrane integrity. Furthermore, the self-assembling AMPDs could bind to bacterial genomic DNA and promote ROS generation, leading to bacterial death via multimodal mechanisms of action. Collectively, this work elucidates the effects of hydrophobic group modifications on the structure and activity of AMPDs, and reveals the self-assembly and antimicrobial mechanism of self-assembling AMPDs, providing theoretical basis and guidance for the development of peptide-based antimicrobial nanomaterials.

Curdlan demonstrates significant biological activities and exhibits functional properties such as thickening, water retention, and gelling capabilities. However, the inherent structural simplicity and constrained functionality of pure curdlan-based hydrogels present significant limitations for their utilization in specialized applications requiring multifunctional properties. In this study, curdlan were used as the matrix to prepare multifunctional hydrogels with photothermal conversion, antibacterial and antioxidant capabilities through the addition of tannic acid and iron ions and by employing heating-annealing approach. The molecular interactions between tannic acid and curdlan were elucidated systematically, and the detailed characterization of the hydrogel's functional properties, encompassing its rheological characteristics, thermal stability, swelling kinetics, photo- thermal conversion capability, and biological activities including antioxidant capacity and antimicrobial efficacy were investigated. The results demonstrated that tannic acid formed stable hydrogen-bonding interactions with curdlan molecules, which significantly affected the structural reorganization of curdlan's triple-helix architecture during renaturation. After introducing the Fe3 +, the iron-tannic acid chelation complex was served as an effective cross-linking agent for curdlan polymer chains, resulting in enhanced mechanical strength of the composite hydrogel while simultaneously imparting remarkable photothermal conversion efficiency to the material system. And the composite hydrogel demonstrated significant free radical scavenging capacity, potent antibacterial activity, and good cell compatibility. The developed composite hydrogel including superior antioxidant activity, effective antibacterial performance, and efficient photothermal conversion capability, shows the potential as a promising candidate for wound dressing, thereby significantly expanding the potential utilization of curdlan-based biomaterials.

Cecropin A (1–7) is a cationic antimicrobial peptide which contain lots of basic amino acids. To understand the effect of basic amino acids on cecropin A (1–7), analogues CA2, CA3 and CA4 which have more arginine or lysine at the N-terminal or C-terminal were designed and synthesized. The interaction of cecropin A (1–7) and its analogs with DNA was studied using ultraviolet–visible spectroscopy, fluorescence spectroscopy and circular dichroism spectroscopy. Multispectral analysis showed that basic amino acids improved the interaction between the analogues and DNA. The interaction between CA4 and DNA is most pronounced. Fluorescence spectrum indicated that Ksv value of CA4 is 1.19 × 105 L mol−1 compared to original peptide cecropin A (1–7) of 3.73 × 104 L mol−1. The results of antimicrobial experiments with cecropin A (1–7) and its analogues showed that basic amino acids enhanced the antimicrobial effect of the analogues. The antimicrobial activity of CA4 against E. coli was eightfold higher than that of cecropin A (1–7). The importance of basic amino acid in peptides is revealed and provides useful information for subsequent studies of antimicrobial peptides.

RAD51 is a core factor for homologous recombination (HR) to repair DNA double strand breaks and overexpressed in breast cancer cells. Truncated peptide BRC4 (1523-1537) was obtained by computer simulation which had the highest binding free energy targeting RAD51. To enhance the binding affinity to the target protein, six nicotinic acid derivatives were modified at the N-terminal of BRC4 (1523-1537) by Fmoc solid-state synthesis to obtain nicotinamide-modified peptides. The interaction of RAD51 (181-200) with BRC4 (1523-1537) and nicotinamide-modified peptides were verified by circular dichroism (CD) spectroscopy and fluorescence spectroscopy. In conclusion, modifying small molecule pharmacophores can improve binding ability. According to spectral results, 2-chloro-5-fluoronicotinic acid modified BRC4 (1523-1537) has the most significant influence on the secondary structure of RAD51 (181-200); binding constant is 1.1×10 L·mol . Cell experiments showed that BRC4 (1523-1537) modified with nicotinic acid N-oxide had the best inhibitory effect on the proliferation of MDA-MB-231 cells.

Based on the typical similar repeat units (abcdefg)n of α-helical structure, the peptide H was designed to self-assemble into an organohydrogel in response to pH. Depending on the different pH, the proportions of secondary structure, microstructure, and mechanical properties of the gel were investigated. Circular dichroism (CD) and Fourier transform infrared (FT-IR) showed that the proportion of α-helical structure gradually increased to become dominant with the increase of pH. Combining transmission electron microscopy (TEM) and atomic force microscopy (AFM), it was found that the increase of the ordered α-helix structure promoted fiber formation. The further increase in pH changed the intermolecular forces, resulting in an increase in the α-helix content and the enhancement of helix-helix interaction, causing the gel fibers to converge into thicker and more dense ones. The temperature test showed the stable rheological properties of the organohydrogel between 20-60 °C. Drug release and cytotoxicity showed that the DOX-loaded organohydrogel could have a better release in an acidic environment, indicating its potential application as a drug local delivery carrier.

Two peptide-carbazole conjugates, CTAT and CNLS, were designed and synthesized using carbazole Schiff base to modify the cell membrane penetrating peptide TAT (47-57) and the nuclear localization peptide NLS at the N terminus. The interaction with ctDNA was investigated by multispectral and agarose gel electrophoresis. And the effects of CNLS and CTAT on the G-quadruplex structure were explored by circular dichroism titration experiments. The results show that both CTAT and CNLS interact with ctDNA in a minor groove binding manner. Both conjugates bind more tightly to DNA than the individual substances CIBA, TAT and NLS. In addition, CTAT and CNLS are capable of unfolding parallel G-quadruplex structures and are potential G-quadruplex unfolding agents. Finally, broth microdilution was performed to test the antimicrobial activity of the peptides. The results showed that CTAT and CNLS had a 4-fold increase in antimicrobial activity compared with the parent peptides TAT and NLS. They could exert antimicrobial activity by disrupting the integrity of cell membrane bilayer and binding to DNA, and could be used as novel antimicrobial peptides for the development of novel antimicrobial antibiotics.

The widespread conversion of synthetic receptors into luminescent sensors has been achieved via the use of fluorescent-indicator displacement assays (F-IDAs). Due to their rigid structures and efficient binding affinities, cucurbit[n]urils, combined with a variety of fluorescent guests, have gained extensive utilization in fluorescent-indicator displacement assays for sensing non-fluorescent or weakly fluorescent organic compounds (analytes) in a selective and specific manner. This mini-review summarizes recent advances in the design of cucurbit[n]uril-based fluorescent-indicator displacement assays and discusses the current challenges and future prospects in this area.

Various peptide drugs have entered the market with the development of molecular biology. Peptide drugs are used for treat diseases such as diabetes, breast cancer, and HIV infection. In this study, three nicotinamide-modified peptides were synthesized by modifying the N-terminus of BRCA1 (856-871, Y856R, K862Y, R866W) peptide with three nicotinic acid derivatives using solid-phase peptide synthesis. The results of calf thymus DNA (ctDNA) binding activity indicated that binding constants of BRCA1 (856-871, Y856R, K862Y, R866W) (P0) and three nicotinamide-modified peptides (P1, P2, and P3) to ctDNA were 1.89 x 10(3), 2.97 x 10(4), 7.61 x 10(4), and 8.09 x 10(4) L.mol(-1), respectively. The binding affinity of the modified peptides was superior to that of BRCA1 (856-871, Y856R, K862Y, R866W). Delta H-theta < 0 and Delta S-theta < 0 indicated that van der Waals force and hydrogen bond contributed most to peptide-ctDNA binding. Results obtained by Circular dichroism (CD) indicated that peptide binding interaction led to conformational changes in ctDNA. Ultraviolet-visible (UV) spectroscopy, ethidium bromide (EB) competition experiments, DNA melting experiments, and viscosity measurements verified that peptides interacted with ctDNA via groove binding. Ionic strength experiments manifested that electrostatic binding was also involved in peptide-ctDNA binding.

The mutation in breast cancer susceptibility gene 2 (BRCA2) is often accompanied by a p53 mutation, the interaction between highly conserved BRC motifs in BRCA2 and p53 was found in cancer progression. For understanding the interaction mechanism of p53 and BRC motifs, the key segment of p53, p53(171-192), was selected as the target, and the spatial structure of p53(171-192)/BRC3 was simulated using computing platform "Discovery studio 2016" and CABS-dock server plat to provide the basis for designing BRC analogs. Polypeptides were purified by HPLC in high purity after synthesized through solid-phase method. Circular dichroism spectroscopy was used to investigate interaction between the BRC peptides and p53(171-192). The results showed that the N-terminus of BRC3 interacted with p53(171-192), but the mutations in helix structure of BRC3 significantly affected the solubility of mutants, which may influence on the interaction of the BRC analogs and p53(171-192). The results also indicated that the structure and action site of BRC3 were different from that of BRC2, having a difference in the interaction role of p53. And may provide some helpful information regarding active polypeptides targeting p53, and inspire the rational design of active polypeptides.(c) 2022 Elsevier B.V. All rights reserved.