bims-cepepe Biomed News
on Cell-penetrating peptides
Issue of 2025–07–20
twenty-one papers selected by
Henry Lamb, Queensland University of Technology



  1. Methods Mol Biol. 2025 ;2934 95-103
      Macrocyclic peptides, known for their high specificity, binding affinity, and potential membrane permeability, represent a promising modality in drug discovery, particularly for intracellular targets deemed undruggable by conventional small molecules. Traditional methods for macrocycle synthesis often involve labor-intensive purification steps, limiting throughput and scalability. This protocol presents a streamlined approach for the synthesis of large macrocyclic peptide libraries, utilizing solid-phase peptide synthesis (SPPS) followed by purification-free cyclization of linear dithiol peptides in high-throughput array formats. The workflow incorporates automated peptide synthesis, efficient resin preparation, and thioether cyclization strategies, enabling the generation of diverse libraries suitable for screening campaigns. Key features include the use of bis-electrophilic linkers for cyclization, quality control via LC-MS, and optional concentration assays. This robust method accelerates the development of macrocyclic libraries, facilitating the discovery of drug candidates targeting challenging biomolecular interactions.
    Keywords:  Combinatorial libraries; Cyclic peptides; High-throughput experimentation; Macrocycles
    DOI:  https://doi.org/10.1007/978-1-0716-4578-9_7
  2. Methods Mol Biol. 2025 ;2934 59-70
      Cyclic peptides have emerged as promising therapeutic agents for targeting challenging protein-protein interactions (PPIs), combining high affinity, specificity, stability, and potential for improved drug-like properties. The outlined protocol describes a streamlined method for side chain-to-side chain lactam cyclization in a peptide array format based on the μSPOT method. The approach enables efficient synthesis and screening of cyclic peptide libraries with minimal synthetic effort, focusing on exploring cyclization positions and linker topology. The method is exemplified by developing cyclic peptide modulators of the APP/Mint2 PPI, a target implicated in Alzheimer's disease. The workflow integrates orthogonal protection strategies, analytical controls, and array-based binding assays, enabling the identification of binding-optimized cyclic peptides. Follow-up validation through fluorescence polarization assays demonstrated a strong correlation with array-based relative binding data (r2 = 0.88). The described approach is versatile and scalable, offering a robust platform for discovering novel cyclic peptides with enhanced stability, affinity, and permeability, paving the way for advanced therapeutic applications in PPI modulation.
    Keywords:  Lactam cyclization; PPIs; Peptide arrays; Stapling; μSPOT
    DOI:  https://doi.org/10.1007/978-1-0716-4578-9_5
  3. Methods Mol Biol. 2025 ;2934 245-273
      This protocol details the use of yeast surface display technology for the in vitro-directed evolution of disulfide-tethered macrocyclic peptide ligands. In the first section, we describe the generation of large naïve combinatorial libraries encoding cysteine-rich peptide sequences expressed on the yeast cell surface using homologous recombination-based methods. In the second section, we detail the use of fluorescence-activated cell sorting to rapidly and effectively isolate yeast-encoding disulfide-tethered macrocyclic peptide ligands with favorable binding properties. In the last section, we describe the quantitative characterization of isolated disulfide-tethered macrocyclic peptide ligand variants directly as yeast cell surface fusions, thus eliminating the need for costly and time-consuming synthesis and purification.
    Keywords:  Cyclic peptide; Directed evolution; Disulfide-tethered macrocyclic peptide; Drug discovery; High-throughput screening; Yeast surface display
    DOI:  https://doi.org/10.1007/978-1-0716-4578-9_17
  4. ACS Synth Biol. 2025 Jul 13.
      Peptide libraries present have improved means to effectively identify epitopes of antibodies, either as monoclonal reagents or polyclonal constituents of the immune response, which includes characterization of vaccination responses, profiling of allergic reactions, and screening of patient samples for autoantibodies. In all of these examples, there is an urgent demand for simple and inexpensive target epitope screening. Here, we present a method for epitope identification, based on the yeast display of overlapping peptides conformationally constrained within the Levivirus capsid protein PP7 with the aid of a disulfide bridge. Using rituximab as a model antibody, the PP7 scaffold was screened for favorable positions for the grafting of peptides, which should allow high accessibility and efficient cyclization. Libraries of overlapping peptide fragments were then constructed, affinity-selected, and screened to retrieve the correct epitopes of model monoclonal antibodies through the enrichment of affinity-captured sequences. Further, plasma rich in antiglutamic acid decarboxylase (GAD) 65 antibodies, a phenomenon associated with a number of neurological disorders, such as "stiff-person-syndrome", was successfully used as a bait to discover the relevant epitope from the antigen peptide library. The presented system sets the basis for a platform that could contribute to novel diagnostic approaches and the discovery of antigen-specific treatments, conducive to a precision medicine approach superior to generalized immunosuppression.
    Keywords:  antibody−antigen interaction; autoantibodies; cyclic peptides; epitope mapping; neurological disease; yeast display
    DOI:  https://doi.org/10.1021/acssynbio.4c00873
  5. Eur J Pharm Sci. 2025 Jul 15. pii: S0928-0987(25)00203-9. [Epub ahead of print] 107204
      Cell-penetrating peptides are widely used in drug delivery for their ability to facilitate the transport of nanomaterials inside the cell. We previously studied the gH-625 for its ability to cross cell membranes, delivering various cargos into different cell types. In this study, since gH-625 suffers from low proteolytic stability, we identified the main cleavage sites after incubation with the enzyme chymotrypsin, and L-amino acids at these sites were replaced with their D-enantiomers, which share similar physicochemical properties but have distinct biological roles. Four peptides, namely gH-w10, gH-l7, gH-y13, and gH-combi, were designed and synthesized. Their biosafety profiles were evaluated in both normal and cancer cell lines and no significant toxic effects were revealed at the tested concentrations. Subsequently, we assessed their cell-penetrating ability by evaluating cellular uptake through fluorescence microscopy and investigated their mechanism of action in a model system of liposomes, measuring fusogenic activity, peptide insertion into the lipid bilayer, and leakage activity. The impact of the D-amino acid substitution on secondary structure was explored by circular dichroism and nuclear magnetic resonance studies. Finally, in vitro safety profiling data of the gH-625 and its most promising derivative gH-combi were further confirmed in vivo using a chicken embryo model.
    Keywords:  cell-penetrating peptide; in ovo toxicity; membrane interaction
    DOI:  https://doi.org/10.1016/j.ejps.2025.107204
  6. Methods Mol Biol. 2025 ;2934 41-56
      Protein-protein interactions (PPIs) are crucial in many diseases but are often considered "undruggable," in particular when involving intracellular proteins. Frequently, their large, shallow surfaces cannot be engaged by classic small molecules. Instead, peptide-based approaches have shown promise, offering antibody-like surface recognition with improved cellular uptake. Notably, structurally highly relevant, β-sheet-derived hairpins have not been much explored as PPI inhibitors. These structures, consisting of antiparallel β-strands connected by short turns, are stabilized by interstrand hydrogen bonds and turn-inducing amino acids. Stabilized and cyclic versions potentially have superior binding and uptake properties. This chapter examines strategies for stabilizing β-hairpins, including β-turn design, macrocyclization, and crosslinking, to enhance not only their binding affinity but also cellular uptake and biostability.
    Keywords:  Interstrand crosslinks; Peptidomimetic; Protein-protein interaction; β-hairpin; β-turnβ-turn
    DOI:  https://doi.org/10.1007/978-1-0716-4578-9_4
  7. Front Chem. 2025 ;13 1637329
      Disulfide bonds are indispensable structural motifs in bioactive peptides, stabilizing conformations which are critical for molecular recognition and biological activity. However, their intrinsic chemical lability under physiological and manufacturing conditions has long presented challenges in peptide drug development. Efforts to address these limitations have yielded a diverse array of disulfide bond surrogates, each with distinct advantages and constraints. Among these, methylene thioacetal linkages have recently emerged as a particularly promising method offering a favorable balance of structural fidelity, synthetic accessibility, and chemical stability. This review summarizes the biological importance and limitations of native disulfide bonds, surveys established strategies for disulfide bond mimicry, and provide a comprehensive summary of research leveraging methylene thioacetal chemistry as an emerging tool in the design of next-generation peptide therapeutics.
    Keywords:  disulfide surrogate; methylene thioacetal bond; peptide drug discovery; peptide synthesis; stability and bioactivity
    DOI:  https://doi.org/10.3389/fchem.2025.1637329
  8. Methods Mol Biol. 2025 ;2934 71-93
      The library of one type of cyclic peptide immobilized on a gel-type bead (OPOB) is a powerful tool for the discovery of interacting peptides. Hydrophilic, water-swellable beads are particularly well suited for bioassays with bead-bound peptides in aqueous media, particularly with targets such as whole living cells. The library is constructed by the "split and combine method." The key issues of successful discovery are both the quality of individual peptides on beads and the uniformity of each split batch. Two types of OPOBs have been proposed. Natural and non-natural amino acids, 19 and 5 respectively, have been used as building blocks to generate the diversity of ca. 200 million hexapeptides with cysteinyl residues forming the cyclic peptides. Selected beads after screening were sequenced initially by conventional Edman degradation, although this was time-consuming and several problems are known. To resolve these, partial acid hydrolysis with 5.7 mol/L hydrogen chloride followed by LC/MS has been proposed. In addition to the cyclic form prepared via the disulfide of cysteinyl residues, a thioether linkage was also considered. For a second generation of libraries, a methionine residue was inserted for the site-specific rapid cleavage by cyanogen bromide to liberate the immobilized peptides allowing high-throughput characterization by MALDI-TOF-MS/MS without LC purification. Peptides discovered from these libraries can be built into affinity probes for target purification, as well as cell-targeting constructs for cell-specific staining or delivery of diverse cargos, which has been designated "peptide-vehicle" for therapy.
    Keywords:  Cell targeting; Cyclic peptide library; Drug discovery; Mass spectrometry; One-peptide-on-one-bead; Peptide vehicle; Sequence analysis
    DOI:  https://doi.org/10.1007/978-1-0716-4578-9_6
  9. Methods Mol Biol. 2025 ;2934 181-187
      Peptides and peptide libraries are valuable probes in solid-phase binding assays and widely used in studies of protein-protein interactions. However, a high unspecific background can disturb or even inhibit a successful experiment. We describe an easy and flexible method for pre-purification of samples that is particularly well-suited for high-throughput processing of large numbers of samples.
    Keywords:  Background elimination; Peptide libraries; Solid-phase binding assay
    DOI:  https://doi.org/10.1007/978-1-0716-4578-9_13
  10. Methods Mol Biol. 2025 ;2934 275-291
      Cystine-knot peptides, with their exceptional thermal stability and resistance to proteolytic degradation, present highly favorable biophysical properties for use as scaffolds in engineering of binders for diverse applications. Multiple variants of knottins with prescribed functional characteristics were described in the literature. These were obtained by rational engineering of natural peptides or by combinatorial library screening. Herein, we describe in detail an ultra-high-throughput screening method of cystine-rich peptide libraries making use of yeast surface display. This is exemplified by converting a trypsin-like protease inhibiting oMCoTI-II cystine-knot framework to a binder of the immune-oncology target CTLA-4. Combinatorial library cloning, followed by yeast surface presentation and sorting, analysis of single clones, and finally chemical synthesis of cystine-knot peptides and their functional validation, provides a robust method for obtaining cystine-rich peptides with novel functional characteristics.
    Keywords:  Cystine knots; Flow cytometry; Peptide inhibitor; Peptide library; Yeast surface display
    DOI:  https://doi.org/10.1007/978-1-0716-4578-9_18
  11. bioRxiv. 2025 Jun 17. pii: 2025.06.13.659569. [Epub ahead of print]
      Peptides are desirable therapeutics due to their inherent potency, safety, cost-effectiveness and ability to engage large or more complex protein surfaces. Slower kinetics of protein-peptide (un)binding can directly influence their drug efficacy and duration of action, in part by improving plasma stability of the peptide. The CLR:RAMP1 complex and its endogenous agonist peptide CGRP are of particularly high interest because of their central role in migraine pathophysiology. A better understanding of peptide binding mechanisms is needed for the development of next-generation peptide-based drugs with optimized kinetic properties. In this study, we comparatively analyze constructs of native CGRP and "ssCGRP", an engineered variant with 430-fold longer residence time on the CLR:RAMP1 complex. Using large-scale computational resources and our high-dimensional weighted-ensemble algorithm, we then thoroughly sample and compare unbinding path ensembles for the two peptides. This elucidates the basis of the engineered residence time enhancement for ssCGRP and provides a detailed view of the intra- and intermolecular stabilizing interactions for both peptides in the bound ensemble and along the unbinding transition path. The bias-free nature of the sampling approach in combination with Markov state modeling allows for the calculation of committor values and the first analysis of protein-peptide binding transition state ensembles. Through analysis of the unbinding committor, we find that ssCGRP(27-37) also demonstrates enhanced ligand recapture of intermediate unbinding conformations and samples a more heterogeneous bound-state ensemble that entropically stabilizes the bound basin. This study shows the molecular determinants of peptide residence time at CLR:RAMP1 and provides valuable insight for the design of long-acting peptide therapeutics.
    DOI:  https://doi.org/10.1101/2025.06.13.659569
  12. Methods Mol Biol. 2025 ;2934 233-243
      Peptide libraries, especially those featuring cyclic and other modified variants, are central in drug discovery and chemical biology. Traditional methods for their generation often rely on labor-intensive synthetic approaches with limited diversity or enzyme-mediated conversions, which are constrained by substrate specificity, scalability challenges, complex biosynthetic systems, and restricted functional group diversity. This mini-review highlights enzymes from ribosomally synthesized and posttranslationally modified peptide (RiPP) gene clusters, an expanding class of biocatalysts, as a alternative enzyme source. RiPP enzymes may address key limitations in modified peptide library production, particularly in cyclization. With regulatable allosteric activities and compatibility with short synthetic peptides under mild conditions, these enzymes could be seamlessly integrated into scalable, high-throughput workflows and in vitro systems. This mini-review provides a perspective on RiPP enzymes through the lens of synthetic peptide library users, exploring their potential for converting synthetic peptide libraries and outlining the key requirements for their broader application in generating chemically diverse, new-to-nature peptide scaffolds.
    Keywords:  Cyclization; Enzymatic catalysis; Peptide library; Posttranslational modification; RiPP enzymes
    DOI:  https://doi.org/10.1007/978-1-0716-4578-9_16
  13. Eur J Med Chem. 2025 Jul 11. pii: S0223-5234(25)00726-3. [Epub ahead of print]297 117961
      Tumour signalling pathways play a pivotal role in tumorigenesis by controlling key cellular processes, including growth, proliferation, metastasis, and survival. Conventional treatments like chemotherapy often face limitations such as non-specific toxicity and drug resistance. Peptide inhibitors have gained attention as a promising therapeutic alternative due to their high selectivity in disrupting oncogenic pathways via protein-protein interactions (PPIs) and ligand binding. Currently, two out of 31 peptide-based cancer drugs have demonstrated signalling inhibition, with several others under investigation. However, challenges related to stability, delivery, and resistance persist, prompting innovations in peptide design, such as cyclisation and nanoparticle-based delivery systems. This review examines strategies to enhance peptide drug efficacy, explores the mechanisms by which peptide inhibitors target key pathways like the rat sarcoma protein (RAS) and mammalian target of rapamycin (mTOR) pathways, and highlights ongoing research on peptide-based interventions. Key examples include RAS-targeting peptides such as KRpep-2D, cyclo-CRVLIR, L5UR, RAS-binding peptide (RBP), the mutant KRAS peptide vaccine combined with Nivolumab and Ipilimumab, cyclorasin B4-27, and LUNA18, as well as mTOR-targeting peptides like P1_WT, PDHK1-241aa, TRIM1-269aa, and the micropeptide human small regulatory polypeptide of amino acid response (hSPAR). Among these, the mutant KRAS peptide vaccine (with Nivolumab and Ipilimumab) and LUNA18 demonstrate promising clinical potential and are currently undergoing trials.
    Keywords:  Cancer; Inhibitors; Peptides; RAS; Signalling pathways; mTOR
    DOI:  https://doi.org/10.1016/j.ejmech.2025.117961
  14. J Phys Chem B. 2025 Jul 15.
      Water, often termed the universal solvent, plays a vital role in numerous biomolecular processes, including protein-protein interactions. These interactions are frequently mediated by water molecules, making their characterization essential for developing therapeutic strategies. One such critical complex is p53-MDM2, which is central to cellular regulation. Inhibiting the p53-MDM2 interaction remains a significant therapeutic challenge, and stapled peptides have emerged as promising candidates in this context. The stapled peptides are peptidomimetics in which the side chains of two suitably positioned amino acids are covalently linked using an appropriate chemical moiety. In this study, we investigate the role of water in the binding of stapled p53 peptides to MDM2 using extensive molecular dynamics simulations. Our aim is to understand how variations in the chemical nature and stapling position of the hydrocarbon cross-linker influence the behavior of water molecules surrounding the p53 peptide. We demonstrate that such modifications significantly alter the structure and dynamics of the surrounding solvent. Using rigorous entropy calculations, we rationalize the enhanced binding affinity of stapled p53 peptides compared to that of their unstapled counterparts from a solvent-centric perspective. Specifically, the entropy gain of water molecules around the stapled peptides, combined with the conformational entropy loss of the peptide, contributes favorably to binding. These findings offer valuable insights into the rational design of stapled peptides and support the development of improved therapeutic inhibitors targeting the p53-MDM2 interaction.
    DOI:  https://doi.org/10.1021/acs.jpcb.5c03100
  15. J Am Chem Soc. 2025 Jul 18.
      Traditional methods for identifying selective protease substrates have primarily relied on synthetic libraries of linear peptides, which offer limited sequence and structural diversity. Here, we present an approach that leverages phage display technology to screen large libraries of chemically modified cyclic peptides, enabling the identification of highly selective substrates for a protease of interest. Our method uses a reactive chemical linker to cyclize peptides on the phage surface, while simultaneously incorporating an affinity tag and a fluorescent reporter. The affinity tag enables capture of the phage library and subsequent release of phages expressing optimal substrates upon incubation with a protease of interest. The addition of a turn-on fluorescent reporter allows direct quantification of cleavage efficiency throughout each selection round. The resulting identified substrates can then be chemically synthesized, optimized and validated using recombinant enzymes and cells. We demonstrate the utility of this approach using Fibroblast Activation Protein α (FAPα) and the related proline-specific protease, dipeptidyl peptidase-4 (DPP4), as targets. Phage selection and subsequent optimization identified substrates with selectivity for each target that have the potential to serve as valuable tools for applications in basic biology and fluorescence image-guided surgery (FIGS). Overall, our strategy provides a rapid and unbiased platform for effectively discovering highly selective, non-natural protease substrates, overcoming key limitations of existing methods.
    DOI:  https://doi.org/10.1021/jacs.5c04424
  16. Peptides. 2025 Jul 12. pii: S0196-9781(25)00091-9. [Epub ahead of print] 171430
      Figainin-2PL (FLGTVLKLGKAIAKTVVPMLTNAMQPKQ.NH2) is active against a range of antibiotic-resistant bacteria as well as human tumor-derived cells. The study aimed to determine the effects of a proline-substitution on the biological potency of the peptide. Secondary structure predictions indicate that figainin-2PL can adopt a helix-turn-helix conformation in membrane-mimetic environments. Circular dichroism spectra are consistent with these predictions. Replacement of the Pro18 residue by either L-Ala, L-Lys or D-Lys increased the extent and stability of the helical domains. All substitutions increased cytotoxic activity against a range of human tumor-derived cells (between 1.5- and 3-fold) but major (between 4- and 10-fold) increases in hemolytic activity against mouse erythrocytes were also observed. While the substitutions Pro18 → L-Ala and Pro18 → L-Ala produced only minor and inconsistent changes in antibacterial activity, the [P18k] analog displayed a 2- to 4-fold greater (MIC and MBC in the range 1- 8µM) against the ESKAPE pathogens Enterococcus faecalis, Enterococcus faecium, Klebsiella pneumoniae and Pseudomonas aeruginosa compared with figainin-2PL and the peptide retained high potency against Acinetobacter baumannii, Escherichia coli, Staphylococcus aureus and Clostridium difficile (MIC and MBC = 2µM). Consequently, the [P18k] peptide shows therapeutic potential for development into a broad-spectrum, topical antimicrobial agent.
    Keywords:  Circular dichroism; Cytotoxicity; Figainin-2PL: Antimicrobial peptide; Frog skin
    DOI:  https://doi.org/10.1016/j.peptides.2025.171430
  17. ACS Pharmacol Transl Sci. 2025 Jul 11. 8(7): 1919-1933
      The development of smart nanoparticles for precision medicine in anticancer drug delivery and controlled release has the potential to revolutionize cancer treatment. This progress is driven by expanding body of preclinical and early clinical studies on anticancer nanoparticles. Despite these advancements, a critical challenge remains achieving a selective and efficient tumor accumulation, along with effective extravasation and deep tissue penetration of nanoparticles into the tumor parenchyma. Affinity targeting strategies using ligands such as homing peptides and antibodies leverage molecular recognition to enhance selectivity, efficacy, and therapeutic activity by directing them to tumor-specific receptors or biomarkers, thereby minimizing off-target effects and improving drug delivery efficiency. Tumor-homing C-end Rule (CendR) peptides, such as prototypic iRGD peptide, represent a promising strategy due to their unique multistep mechanism that facilitates both selective targeting and enhanced tissue penetration. This review highlights key milestones in the evolution of peptide-targeted nanoparticles, underscoring their role in advancing precision nanomedicine.
    Keywords:  C-end Rule peptides; active targeting; homing peptide; iRGD; nanoparticle; precision medicine
    DOI:  https://doi.org/10.1021/acsptsci.5c00241
  18. bioRxiv. 2025 Jun 25. pii: 2025.06.24.661379. [Epub ahead of print]
      De novo protein design has emerged as a powerful strategy with the promise to create new tools. The practical performance of designed fluorophore binders, however, has remained far from meeting fluorescence microscopy demands. Here, we design de novo Rhodamine Binder (Rhobin) tags that combine ideal properties including size, brightness, and now adding hyperstability. Rhobin allows live and fixed cell imaging of a wide range of subcellular targets in mammalian cells. Its reversible fluorophore binding further enables live super-resolution STED microscopy with low photobleaching, as well as PAINT-type single-molecule localization microscopy. We showcase Rhobin in the extremophile Sulfolobus acidocaldarius living at 75°C, an application previously inaccessible by existing tags. Rhobin will serve as the basis for a new class of live cell fluorescent tags and biosensors.
    DOI:  https://doi.org/10.1101/2025.06.24.661379
  19. Bioorg Med Chem. 2025 Jul 11. pii: S0968-0896(25)00244-5. [Epub ahead of print]129 118303
      This study proposes a machine learning-based peptide screening strategy for identifying wheat-derived peptides with anti-caries potential. By integrating multiple feature descriptors and algorithms (Random Forest, XGBoost), we constructed a Screening Funnel Model and identified a wheat-derived peptide AP-2 (FPVTWRWWKWW) as the prioritized candidate. Experimental validation demonstrated that AP-2 exhibits potent antibacterial activity against Streptococcus mutans (MIC = 4 μM), achieving rapid bactericidal effects through bacterial membrane disruption, and significantly inhibits biofilm formation at 1/2 × MIC concentration. AP-2 exhibited an extremely low hemolysis rate and demonstrated favorable stability in saliva within 1 h. In vivo, studies confirmed that AP-2 effectively prevents early caries formation in rats at low concentrations without inducing organ toxicity or oral microbiota dysbiosis. These results demonstrate the utility of machine learning in discovering wheat-derived anti-caries peptides and indicate that AP-2 represents a safe and effective candidate for clinical translation.
    Keywords:  Antimicrobial peptides; Biocompatibility; Caries prevention; Dental caries; Machine learning; Streptococcus mutans
    DOI:  https://doi.org/10.1016/j.bmc.2025.118303
  20. J Enzyme Inhib Med Chem. 2025 Dec;40(1): 2522810
      Aberrant expression of PLK1 and PLK4 is closely associated with tumourigenesis, and their simultaneous inhibition can effectively suppress tumour proliferation. In this study, we successfully identified peptide inhibitors (Peptides 1-5) capable of simultaneously targeting PLK1-PBD and PLK4-PB3 via pharmacophore-based virtual screening. Binding affinity analyses demonstrated that all candidate peptides exhibited nanomolar binding affinity for both targets. In vitro cancer cell growth inhibition assays revealed that these peptides could suppress the growth of cervical cancer cells. Among them, Peptide-2 showed the optimal binding affinity and anticancer cell proliferative activity (PLK1-PBD: Kd = 8.02 ± 0.16 nM; PLK4-PB3: Kd = 11.32 ± 0.19 nM; IC50 = 0.44 ± 0.03). Molecular dynamics (MD) simulations further predicted that Peptide-2 could stably bind to the binding sites of both PLK1-PBD and PLK4-PB3. This study reported a novel peptide inhibitor Peptide-2 with potent dual-target inhibitory activity against PLK1-PBD/PLK4-PB3, providing a novel strategy for cancer therapy.
    Keywords:  Polo-box domain of polo-like kinase 1 (PLK1-PBD); docking screening; pharmacophore screening; polo-box 3 of PLK4 (PLK4-PB3)
    DOI:  https://doi.org/10.1080/14756366.2025.2522810
  21. Sci Data. 2025 Jul 14. 12(1): 1213
      This paper presents a comprehensive dataset comprising 58,583 experimentally validated therapeutic peptides with annotated structure information. These peptides are grouped into 47 categories based on their function or therapeutic property like antimicrobial or glucose-regulatory, of which 21,130 are multi-function peptides and 54,722 possess structural annotation information. We believe this dataset can be useful for the relevant research of therapeutic peptides, especially for computational tool developments in therapeutic peptide discovery and further exploration of the 'sequence-structure-function' relationship for therapeutic peptides.
    DOI:  https://doi.org/10.1038/s41597-025-05528-1