Multifunctional Peptide Research Articles

AMHF‐TP: Multifunctional therapeutic peptides prediction based on multi‐granularity hierarchical features

AMHF‐TP: Multifunctional therapeutic peptides prediction based on multi‐granularity hierarchical features

IMFP-LG: Identification of Novel Multi-Functional Peptides by Using Protein Language Models and Graph-Based Deep Learning.

Functional peptides are short amino acid fragments that have a wide range of beneficial functions for living organisms. The majority of previous research focused on mono-functional peptides, but a growing number of multi-functional peptides have been discovered. Although there have been enormous experimental efforts to assay multi-functional peptides, only a small fraction of millions of known peptides have been explored. Effective and precise techniques for identifying multi-functional peptides can facilitate their discovery and mechanistic understanding. In this article, we presented a method iMFP-LG for identifying multi-functional peptides based on protein language models (pLMs) and graph attention networks (GATs). Comparison results showed that iMFP-LG outperforms state-of-the-art methods on both multi-functional bioactive peptides and multi-functional therapeutic peptides datasets. The interpretability of iMFP-LG was also illustrated by visualizing attention patterns in pLMs and GATs. Regarding the outstanding performance of iMFP-LG on the identification of multi-functional peptides, we employed iMFP-LG to screen novel candidate peptides with both ACP and AMP functions from millions of known peptides in the UniRef90. As a result, 8 candidate peptides were identified, and 1 candidate that exhibits both antibacterial and anticancer effects was confirmed through molecular structure alignment and biological experiments. We anticipate that iMFP-LG can assist in the discovery of multi-functional peptides and contribute to the advancement of peptide drug design.

A Multifunctional Peptide Nucleic Acid/Peptide Copolymer-Based Dual-Mode Biosensor with Macrophage-Hitchhiking for Enhanced Tumor Imaging and Urinalysis.

Biosensors are capable of diagnosing tumors through imaging in vivoor liquid biopsy, but they face the challenges of inefficient delivery into tumor sites and the lack of reliable tumor-associated biomarkers. Herein, we constructed a dual-mode biosensor based on a multifunctional peptide nucleic acid (PNA)/peptide copolymer and DNA tetrahedron for tumor imaging and urinalysis. The biosensor could enter the cancer cells to initiate a microRNA-21-specific catalytic hairpin assembly reaction after cleavage by matrix-metalloprotease (MMP) in the tumor microenvironment, and the MMP cleavage product was released into the bloodstream and then was filtered out by the kidney. As PNA was a synthetic DNA analogue that could not be degraded by nucleases and proteases, it could serve as a reliable synthetic biomarker and be easily detected by high-performance liquid chromatography in urine. Importantly, the biosensor was hitchhiked on the macrophage membrane to realize efficient delivery in the depth of tumor utilizing the macrophage ability of actively homing to the tumor site and infiltrating into the tumor. The results indicated that the signal output of the biosensor was improved remarkably and mice with a tumor volume as little as 30-40 mm3 could be reliably discriminated through urine assay. This innovative macrophage-hitchhiking dual-mode biosensor holds a great potential as a non-invasive and convenient tool for tumor diagnosis and tumor progression evaluation.

Enhancing Antibacterial Properties of Titanium Implants through Covalent Conjugation of Self-Assembling Fmoc-Phe-Phe Dipeptide on Titania Nanotubes.

Bacterial infections and biofilm formation are significant challenges for medical implants. While titanium nanotube engineering improves biocompatibility, it cannot prevent bacterial adhesion and biofilm formation. Optimizing the biomaterial's surface chemistry is vital for its desired functioning in the biological environment. This study demonstrates the covalent conjugating of the self-assembling dipeptide N-fluorenylmethyloxycarbonyl-diphenylalanine (Fmoc-FF) onto titanium nanotube surfaces (TiNTs) without altering the topography. Fmoc-FF peptides, in conjugation with TiNTs, can inhibit biofilm formation, eradicate pre-existing biofilms, and kill bacteria. This functionalization imparts antibacterial properties to the surface while retaining beneficial nanotube topography, synergistically enhancing bioactivity. Surface characterization by XPS, FT-IR, EDS, and SEM confirmed the successful functionalization. Bacterial adhesion experiments showed a significantly improved antibacterial activity of the functionalized TiNT surfaces. This study opens future possibilities for associating biomedical applications such as cell-cell interactions, tissue engineering, and controlled drug delivery of multifunctional self-assembling short peptides with implant materials through surface functionalization.

TPpred-SC: multi-functional therapeutic peptide prediction based on multi-label supervised contrastive learning

TPpred-SC: multi-functional therapeutic peptide prediction based on multi-label supervised contrastive learning

A Nonfouling Electrochemical Biosensor for Protein Analysis in Complex Body Fluids Based on Multifunctional Peptide Conjugated with PEGlyated Phospholipid.

Developing antifouling biosensors capable of performing robustly in complex human body fluids is crucial for biomarker diagnosis and health monitoring. Herein, an antifouling and highly sensitive and stable biosensor was constructed through the self-assembly of the designed conjugates composed of a multifunctional peptide (MP) and PEGylated distearoylphosphatidylethanolamine (DSPE-PEG). The self-assembly capability of the DSPE-PEG-MP was demonstrated clearly through coarse-grained molecular dynamics simulation and transmission electron microscopy, and it can be effectively self-assembled onto the electrode surface modified with gold nanoparticles. The MP was designed to be antifouling and contained a peptide sequence that can specifically bind the target protein Annexin A1 (ANXA1), and the D-type amino acid composition of MP can enhance its resistance to enzymatic hydrolysis. The unique design of MP, in conjugation with the self-assembly capability of the PEGylated phospholipid DSPE-PEG, enabled the biosensor to exhibit excellent antifouling capability and stability in various complex human body fluids. The biosensor was capable of sensitively and selectively quantifying ANXA1 and achieved a limit of detection down to 0.12 pg mL-1. More importantly, the biosensor demonstrated satisfactory accuracy for ANXA1 detection in clinical serum samples, as verified by the enzyme linked immunosorbent assay (ELISA) kits. It is expected that various antifouling biosensors suitable for application in complex biological environments can be constructed by utilizing the strategy of designing similar DSPE-PEG-MP conjugates.

Application of a modified multifunctional short peptide in the treatment of periodontitis

Periodontitis is a chronic inflammatory disease involving plaque biofilm as a pathogenic factor. Potassium ion plays an important role in cellular homeostasis; a large outflow of potassium may lead to local inflammation progression. In this work, the multifunctional short peptide molecule BmKTX-33 was designed by modifying the BmKTX, a Kv1.3 potassium channel inhibitor. This was to explore its antibacterial properties, capability of maintaining cell ion homeostasis, and bone-forming capacity. The results showed that BmKTX-33 had inhibitory effects on S. gordonii, F. nucleatum, and P. gingivalis. Moreover, BmKTX-33 also inhibited excessive potassium outflow in inflammatory environments. Finally, BmKTX-33 promoted MC3T3-E1 early osteogenesis while suppressing the NLRP3 inflammasome's production. In conclusion, BmKTX-33 not only has antibacterial properties, but also can inhibit the expression of NLRP3 inflammasome and play an anti-inflammatory role.

Highly stable and antifouling solid-contact ion-selective electrode for K+ detection in complex system based on multifunctional peptide and conductive MOF

Highly stable and antifouling solid-contact ion-selective electrode for K+ detection in complex system based on multifunctional peptide and conductive MOF

Dendritic cells pulsed with multifunctional Wilms’ tumor 1 (WT1) peptides combined with multiagent chemotherapy modulate the tumor microenvironment and enable conversion surgery in pancreatic cancer

BackgroundWe aimed to develop a chemoimmunotherapy regimen consisting of a novel Wilms’ tumor 1 (WT1) peptide-pulsed dendritic cell (WT1-DC) vaccine and multiagent chemotherapy and to investigate the safety, clinical outcomes,...

Exploration of multi-functional peptides with bioactive and flavorful properties in Inner Mongolian cheese by peptidomics and bioinformatics

Exploration of multi-functional peptides with bioactive and flavorful properties in Inner Mongolian cheese by peptidomics and bioinformatics

Angiogenesis and multiple myeloma: Exploring prognostic potential of adrenomedullin.

Adrenomedullin (AM) is a multifunctional peptide which under basal conditions mainly regulates vasodilation and maintains vascular integrity but is also implicated in the pathogenesis of several malignancies, including multiple myeloma (MM). It has been shown that adrenomedullin is expressed by human myeloma cell lines and that it enhances MM-driven angiogenesis. However, the clinical impact of AM remains unknown. On that basis, we enrolled 32 newly diagnosed multiple myeloma patients (NDMM) and studied the potential of AM as a prognostic biomarker. We report that elevated levels of AM trend with suboptimal treatment response and inferior survival of NDMM patients.

Role of Cathelicidins in Atherosclerosis and Associated Cardiovascular Diseases

Cathelicidins (human LL-37 and rat CRAMP) are multifunctional peptides involved in various cardiovascular conditions. This review integrates the recent findings about the functional involvement of LL-37/CRAMP across atherosclerosis, acute coronary syndrome, myocardial infarction, heart failure, diabetic cardiomyopathy, and platelet aggregation/thrombosis. In atherosclerosis, LL-37 interacts with scavenger receptors to modulate lipid metabolism and binds with mitochondrial DNA and lipoproteins. In acute coronary syndrome, LL-37 influences T cell responses and mitigates calcification within atherosclerotic plaques. During myocardial infarction and ischaemia/reperfusion injury, LL-37/CRAMP exhibits dual roles: protecting against myocardial damage through the AKT and ERK1/2 signalling pathways, while exacerbating inflammation via TLR4 and NLRP3 inflammasome activation. In heart failure, LL-37/CRAMP attenuates hypertrophy and fibrosis via NF-κB inhibition and the activation of the IGFR1/PI3K/AKT and TLR9/AMPK pathways. Moreover, in diabetic cardiomyopathy, these peptides alleviate oxidative stress and fibrosis by inhibiting TGFβ/Smad and AMPK/mTOR signalling and provide anti-inflammatory effects by reducing NF-κB nuclear translocation and NLRP3 inflammasome formation. LL-37/CRAMP also modulates platelet aggregation and thrombosis through the FPR2 and GPVI receptors, impacting apoptosis, autophagy, and other critical cellular processes. This comprehensive overview underscores LL-37/CRAMP as a promising therapeutic target in cardiovascular diseases, necessitating further elucidation of its intricate signalling networks and biological effects for clinical translation.

Low Levels of Adropin Predict Adverse Clinical Outcomes in Outpatients with Newly Diagnosed Prediabetes after Acute Myocardial Infarction.

Adropin-a multifunctional peptide with tissue-protective capacity that regulates energy homeostasis, sensitivity to insulin and inflammatory response-seems to show an inverse association with the presence of cardiovascular and renal diseases, obesity and diabetes mellitus in the general population. The purpose of the study is to elucidate whether adropin may be a plausible predictive biomarker for clinical outcomes in post-ST elevation of myocardial infarction (STEMI) patients with newly diagnosed prediabetes according to the American Diabetes Association criteria. A total of 1214 post-STEMI patients who received percutaneous coronary intervention were identified in a local database of the private hospital "Vita Center" (Zaporozhye, Ukraine). Between November 2020 and June 2024, we prospectively enrolled 498 patients with prediabetes in this open prospective cohort study and followed them for 3 years. The combined clinical endpoint at follow-up was defined as cardiovascular death due to acute myocardial infarction, heart failure, sudden death due to arrhythmia or cardiac surgery, and/or all-cause death. We identified 126 clinical events and found that serum levels of adropin < 2.15 ng/mL (area under the curve = 0.836; 95% confidence interval = 0.745-0.928; sensitivity = 84.9%; specificity = 72.7%; likelihood ratio = 3.11; p = 0.0001) predicted clinical outcomes. Multivariate logistic regression showed that a Gensini score ≥ 32 (Odds ratio [OR] = 1.07; p = 0.001), adropin ≤ 2.15 ng/mL (OR = 1.18; p = 0.001), use of SGLT2i (OR = 0.94; p = 0.010) and GLP-1 receptor agonist (OR = 0.95; p = 0.040) were independent predictors of clinical outcome. Kaplan-Meier plots showed that patients with lower adropin levels (≤2.15 ng/mL) had worse clinical outcomes compared to patients with higher adropin levels (>2.15 ng/mL). In conclusion, low levels of adropin (≤2.15 ng/mL) independently predicted clinical outcomes in post-STEMI patients with newly detected prediabetes and improved the discriminative ability of the Gensini score for 3-year follow-up events. Future clinical studies are needed to clarify whether adropin is a promising molecule to be incorporated into conventional risk scores for the prediction of MACCEs after STEMI.

Screening and Exploring the Application of the Multifunctional Antioxidant Peptides MSWLC and TSWLC.

In this study, an antioxidant pentapeptide library is created based on antioxidant characteristics. The peptides are then purified and separated using liquid chromatography/mass spectrometry (LC/MS) and time-of-flight mass spectrometry (TOF). Chemical evaluations identify four peptides with excellent antioxidant activity. The four peptides undergo biocompatibility testing with L-929, NIH 3T3, and Hep-G2 cells. A model of hydrogen peroxide-induced cellular damage in G2 cells shows the peptides' protective and reparative effects against oxidative damage. Two peptides, MSWLC and TSWLC, which perform best overall, are chosen for further analysis. To explore the peptides' potential multifunctionality, acute liver inflammation, keratitis, and aging models are established in mice. MSWLC and TSWLC demonstrate anti-inflammatory and anti-aging properties. An antioxidant emulsion prepared by emulsification is found to be non-irritant in a mouse skin irritation test. In a mouse model exposed to ultraviolet radiation, the sunscreen exhibits excellent UV protection and antioxidant effects. These peptides possess potent antioxidant properties and multifunctionality, indicating broad application potential.

Functionalization of Alginate Hydrogels with a Multifunctional Peptide Supports Mesenchymal Stem Cell Adhesion and Reduces Bacterial Colonization.

Hydrogels with cell adhesive moieties stand out as promising materials to enhance tissue healing and regeneration. Nonetheless, bacterial infections of the implants represent an unmet major concern. In the present work, we developed an alginate hydrogel modified with a multifunctional peptide containing the RGD cell adhesive motif in combination with an antibacterial peptide derived from the 1-11 region of lactoferrin (LF). The RGD-LF branched peptide was successfully anchored to the alginate backbone by carbodiimide chemistry, as demonstrated by 1H NMR and fluorescence measurements. The functionalized hydrogel presented desirable physicochemical properties (porosity, swelling and rheological behavior) to develop biomaterials for tissue engineering. The viability of mesenchymal stem cells (MSCs) on the peptide-functionalized hydrogels was excellent, with values higher than 85 % at day 1, and higher than 95 % after 14 days in culture. Moreover, the biological characterization demonstrated the ability of the hydrogels to significantly enhance ALP activity of MSCs as well as to decrease bacterial colonization of both Gram-positive and Gram-negative models. Such results prove the potential of the functionalized hydrogels as novel biomaterials for tissue engineering, simultaneously displaying cell adhesive activity and the capacity to prevent bacterial contamination, a dual bioactivity commonly not found for these types of hydrogels.

Biochemical Characterization and Application of Zearalenone Lactone Hydrolase Fused with a Multifunctional Short Peptide.

Zearalenone (ZEN) is an estrogenic mycotoxin causing reproductive toxicity in livestock. Currently, lactone hydrolases are used in the enzymatic degradation of ZEN. However, most lactone hydrolases suffer from low degradation efficiency and poor thermal stability. ZHD518, as a documented neutral enzyme for ZEN degradation, exhibits high enzymatic activity under neutral conditions. In this study, a multifunctional peptide S1v1-(AEAEAHAH)2 was fused to the N-terminus of ZHD518. Compared with the wild-type enzyme, the peptide fusion significantly enhanced protein expression by 1.28 times, enzyme activity by 9.27 times, thermal stability by 37.08 times after incubation at 45 °C for 10 min and enzyme stability during long-term storage. Moreover, ZEN concentrations in corn bran, corn germ meal, and corn gluten powder decreased from 5.29 ± 0.04, 5.31 ± 0.03, and 5.30 ± 0.01 μg/g to 0.48 ± 0.05, 0.48 ± 0.06, and 0.21 ± 0.04 μg/g, respectively, following a 60 min treatment with S1v1-GS-ZHD518, resulting in degradation rates of 90.98, 91.00, and 95.32%, respectively. In conclusion, the properties of S1v1-GS-ZHD518, such as its efficient degradability, high temperature resistance and storage resistance, offer the possibility of its application in food or feed.

In vitro evaluation of multifunctional peptides PW, PF, PPG, PM, IW, and SW for metabolic syndrome management

Multifunctional peptides derived from various food sources, including ancestral grains, hold significant promise for managing metabolic syndrome. These bioactive peptides exhibit diverse properties that collectively contribute to improving the components of metabolic syndrome. In this study, we investigated the in vitro multifunctionality of six peptides (PW, PM, SW, PPG, PW, and IW) identified through in silico analysis and chemically synthesized. These peptides were evaluated for their potential to address metabolic syndrome-related activities such as antidiabetic, antiobesity, antihypertensive, and antioxidative properties. Assessment included their capacity to inhibit key enzymes associated with these activities, as well as their free radical scavenging and cellular antioxidative activities. Principal component analysis was employed to cluster the peptides according to their multifunctionality. Our results revealed that peptides containing tryptophan (SW, PW, and IW) exhibited the most promising multifunctional attributes, with SW showing particularly high potential. This multifunctional peptide represents a promising avenue for addressing metabolic syndrome.

NIR Light and GSH Dual-Responsive Upconversion Nanoparticles Loaded with Multifunctional Platinum(IV) Prodrug and RGD Peptide for Precise Cancer Therapy.

Platinum(II) drugs as a first-line anticancer reagent are limited by side effects and drug resistance. Stimuli-responsive nanosystems hold promise for precise spatiotemporal manipulation of drug delivery, with the aim to promote bioavailability and minimize side effects. Herein, a multitargeting octahedral platinum(IV) prodrug with octadecyl aliphatic chain and histone deacetylase inhibitor (phenylbutyric acid, PHB) at axial positions to improve the therapeutic effect of cisplatin was loaded on the upconversion nanoparticles (UCNPs) through hydrophobic interaction. Followed attachment of DSPE-PEG2000 and arginine-glycine-aspartic (RGD) peptide endowed the nanovehicles with high biocompatibility and tumor specificity. The fabricated nanoparticles (UCNP/Pt(IV)-RGD) can be triggered by upconversion luminescence (UCL) irradiation and glutathione (GSH) reduction to controllably release Pt(II) species and PHB, inducing profound cytotoxicity. Both in vitro and in vivo experiments demonstrated that UCNP/Pt(IV)-RGD exhibited remarkable antitumor efficiency, high tumor-targeting specificity, and real-time UCL imaging capacity, presenting an intelligent platinum(IV) prodrug-loaded nanovehicle for UCL-guided dual-stimuli-responsive combination therapy.

Characterization of corazonin signaling in a molluscan model species, Lymnaea stagnalis

In recent years, new concepts have emerged regarding the nomenclature, functions, and relationships of different peptide families of the gonadotropin-releasing hormone (GnRH) superfamily. One of the main driving forces for this originated from the emerging evidence that neuropeptides previously called molluscan GnRH are multifunctional and should be classified as corazonin (CRZ). However, research articles still appear that use incorrect nomenclature and attribute the same function to molluscan CRZs as vertebrate GnRHs. The aim of the present study was to further support the recent interpretation of the origin and function of the GnRH superfamily. Towards this goal, we report the characterization of CRZ signaling system in the molluscan model species, the great pond snail (Lymnaea stagnalis). We detected a CRZ-receptor-like sequence (Lym-CRZR) by homology-searching in the Lymnaea transcriptomes and the deduced amino acid sequence showed high sequence similarity to GnRH receptors and CRZ receptors. Molecular phylogenetic tree analysis demonstrated that Lym-CRZR is included in the cluster of molluscan CRZRs. Lym-CRZR transiently transfected into HEK293 cells was found to be localized at the plasma membrane, confirming that it functions as a membrane receptor, like other G protein-coupled receptors. The signaling assays revealed that the previously identified Lym-CRZ neuropeptide stimulated intracellular Ca2+ mobilization in a dose-dependent manner, but not cyclic AMP production, in HEK293 cells transfected with Lym-CRZR. Finally, we demonstrated a wide tissue distribution of Lym-CRZR. These results suggest that Lym-CRZ is a multifunctional peptide and provide further insights into the evolution of the GnRH neuropeptide superfamily. The present study also supports the notion that previously termed molluscan “GnRH” should be classified as “CRZ”.

MFTP-Tool: A Wide &amp; Deep Learning Framework for Multi-Functional Therapeutic Peptides Prediction

Background: The identification and functional prediction of Multifunctional Therapeutic Peptides (MFTP) play a pivotal role in drug discovery, particularly for conditions such as inflammation and hyperglycemia. Current computational methods exhibit limitations in their ability to accurately predict the multifunctionality of these peptides. Methods: We propose a novel Wide and Deep Learning Framework that integrates both deep learning and machine learning approaches. The deep learning segment processes word vectors using a neural network model, while the wide segment utilizes the physicochemical properties of peptides in a random forest-based model. This hybrid approach aims to enhance the accuracy of MFTP function prediction. Results: Our framework outperformed the existing PrMFTP predictor in terms of precision, coverage, accuracy, and absolute true values. The evaluation was conducted on both training and independent testing datasets, demonstrating the robustness and generalizability of our model. Conclusion: The proposed Wide &amp; Deep Learning Framework offers a significant advancement in the computational prediction of MFTP functions. The availability of our model through a userfriendly web interface at MFTP-Tool.m6aminer.cn provides a valuable tool for researchers in the field of therapeutic peptide-based drug discovery, potentially accelerating the development of new treatments.