Aggregation Rules of Short Peptides.

The elucidation of aggregation rules for short peptides (e.g., tetrapeptides and pentapeptides) is crucial for the precise manipulation of aggregation.

Controlling Supramolecular Fiber Formation of Nucleopeptide by Guanosine Triphosphate.

Cells use dynamic self-assembly to construct functional structures for maintaining cellular homeostasis. However, using a natural biological small molecule to mimic this phenomenon remains challenging. This work reports the dynamic microfiber formation of nucleopeptide driven by guanosine triphosphate, the small molecule that controls microtubule polymerization in living cells.

Deep Learning Empowers the Discovery of Self-Assembling Peptides with Over 10 Trillion Sequences.

Self-assembling of peptides is essential for a variety of biological and medical applications. However, it is challenging to investigate the self-assembling properties of peptides within the complete sequence space due to the enormous sequence quantities. Here, it is demonstrated that a transformer-based deep learning model is effective in predicting the aggregation propensity (AP) of peptide systems, even for decapeptide and mixed-pentapeptide systems with over 10 trillion sequence quantities.

Retinal Microenvironment-Protected Rhein-GFFYE Nanofibers Attenuate Retinal Ischemia-Reperfusion Injury via Inhibiting Oxidative Stress and Regulating Microglial/Macrophage M1/M2 Polarization.

Retinal ischemia is involved in the occurrence and development of various eye diseases, including glaucoma, diabetic retinopathy, and central retinal artery occlusion. To the best of our knowledge, few studies have reported self-assembling peptide natural products for the suppression of ocular inflammation and oxidative stress. Herein, a self-assembling peptide GFFYE is designed and synthesized, which can transform the non-hydrophilicity of rhein into an amphiphilic sustained-release therapeutic agent, and rhein-based therapeutic nanofibers (abbreviated as Rh-GFFYE) are constructed for the treatment of retinal ischemia-reperfusion (RIR) injury.

Accelerating the prediction and discovery of peptide hydrogels with human-in-the-loop.

The amino acid sequences of peptides determine their self-assembling properties. Accurate prediction of peptidic hydrogel formation, however, remains a challenging task. This work describes an interactive approach involving the mutual information exchange between experiment and machine learning for robust prediction and design of (tetra)peptide hydrogels.

Self-assembled peptides-modified flexible field-effect transistors for tyrosinase detection.

Flexible biosensors have received intensive attention for real-time, non-invasive monitoring of cancer biomarkers. Highly sensitive tyrosinase biosensors, which are important for melanoma screening, remained a hurdle. Herein, high-performance tyrosinase-sensing field-effect transistor-based biosensors (bio-FETs) have been successfully achieved by self-assembling nanostructured tetrapeptide tryptophan-valine-phenylalanine-tyrosine (WVFY) on n-type metal oxide transistors.

Encapsulation of LXR ligand by D-Nap-GFFY hydrogel enhances anti-tumorigenic actions of LXR and removes LXR-induced lipogenesis.

Activation of liver X receptor (LXR) by its ligand T0901317 (T317) enhances interferon-γ (IFNγ) production to inhibit tumor growth. However, induction of severe hypertriglyceridemia and fatty liver by T317 limits its application. The naphthylacetic acid modified D-enantiomeric-glycine-phenylalanine-phenylalanine-tyrosine (D-Nap-GFFY) can form a nanofiber hydrogel which is selectively taken up by antigen-presenting cells (APCs).

Nuclear delivery of dual anticancer drug-based nanomedicine constructed by cisplatinum-induced peptide self-assembly.

Nuclear delivery of anticancer drugs, particularly dual complementary anticancer drugs, can significantly improve chemotherapy efficacy. However, successful examples are rare. We reported a novel dual anticancer drug-based nanomedicine with nuclear accumulation properties.

Preorganization Increases the Self-Assembling Ability and Antitumor Efficacy of Peptide Nanomedicine.

Inspired by the biological process of phosphorylation for which different sites of the same protein may have different activities and functions, we utilized phosphatase-based enzyme-instructed self-assembly (EISA) to construct self-assembled nanomedicine from the precursors with different phosphorylated sites. We found that, although the obtained self-assembling molecules after EISA were identical, the changes of EISA catalytic sites could determine the outcome of molecular self-assembly. The precursor with the phosphorylated site in the middle preorganized before EISA, while the ones with other phosphorylated sites could not preorganize before EISA.

Enhanced cellular uptake and nuclear accumulation of drug-peptide nanomedicines prepared by enzyme-instructed self-assembly.

Subcellular delivery of nanomedicines has emerged as a promising approach to enhance the therapeutic efficacy of anticancer drugs. Nuclear accumulation of anticancer drugs are essential for its therapeutic efficacy because their targets are generally located within the nucleus. However, strategies for the nuclear accumulation of nanomedicines with anticancer drugs rarely reported.

β-Galactosidase instructed supramolecular hydrogelation for selective identification and removal of senescent cells.

The identification and removal of senescent cells is very important to improve human health and prolong life. In this study, we introduced a novel strategy of β-galactosidase (β-Gal) instructed peptide self-assembly to selectively form nanofibers and hydrogels in senescent cells. We demonstrated that the in situ formed nanofibers could alleviate endothelial cell senescence by reducing p53, p21, and p16 expression levels.

Responsive peptide-based supramolecular hydrogels constructed by self-immolative chemistry.

Peptide-based supramolecular hydrogels that are stimuli-responsive under aqueous conditions have many potential biological applications, including drug delivery and sensing. Herein, we reported a series of responsive peptide-based supramolecular hydrogels that respond to glutathione (GSH), nitric oxide (NO) and hydrogen sulfide (HS), which are biologically important signaling molecules. The responsive hydrogelators were designed by "self-immolative" chemistry and constructed by using self-immolative groups to modify short peptides.

A supramolecular hydrogel for spatial-temporal release of auxin to promote plant root growth.

Short peptide-based hydrogels have attracted extensive research interests in drug delivery because of their responsive properties. So far, most drug molecules have been conjugated with short peptides via an amide bond, restricting the release of the native drug molecules. In this study, we demonstrated the effectiveness of an auxin-based hydrogelator linked by a hydrolysable ester bond.

Enzyme-assisted peptide folding, assembly and anti-cancer properties.

The α-helix is the most prevalent conformation in proteins. However, formation of the α-helical conformation remains a challenge for short peptides with less than 5 amino acids. We demonstrated in this study that enzyme-instructed self-assembly (EISA) provides a unique pathway to assist the self-assembly of peptides into the α-helical conformation, while a heating-cooling process leads to a conformation more similar to a β-sheet.

Surface-Induced Hydrogelation for Fluorescence and Naked-Eye Detections of Enzyme Activity in Blood.

Fluorescence probes have been widely applied for the detection of important analytes with high sensitivity and specificity. However, they cannot be directly applied for the detection in samples with autofluorescence such as blood. Herein, we demonstrated a simple but effective method of surface-induced self-assembly/hydrogelation for fluorescence detection of an enzyme in biological fluids including blood and cell lysates.

Multi-responsive supramolecular hydrogels for drug delivery.

We reported in this study a versatile method to prepare multi-responsive supramolecular hydrogels for drug delivery application.