Inhibition of ACE2-S Protein Interaction by a Short Functional Peptide with a Boomerang Structure.

Considering the high evolutionary rate and great harmfulness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is imperative to develop new pharmacological antagonists. Human angiotensin-converting enzyme-2 (ACE2) functions as a primary receptor for the spike protein (S protein) of SARS-CoV-2. Thus, a novel functional peptide, KYPAY (K5), with a boomerang structure, was developed to inhibit the interaction between ACE2 and the S protein by attaching to the ACE2 ligand-binding domain (LBD). The inhibition property of K5 was evaluated via molecular simulations, cell experiments, and adsorption kinetics analysis. The molecular simulations showed that K5 had a high affinity for ACE2 but a low affinity for the cell membrane. The umbrella sampling (US) simulations revealed a significant enhancement in the binding potential of this functional peptide to ACE2. The fluorescence microscopy and cytotoxicity experiments showed that K5 effectively prevented the interaction between ACE2 and the S protein without causing any noticeable harm to cells. Further flow cytometry research indicated that K5 successfully hindered the interaction between ACE2 and the S protein, resulting in 78% inhibition at a concentration of 100 µM. This work offers an innovative perspective on the development of functional peptides for the prevention and therapy of SARS-CoV-2.

Advances in peptide-based drug delivery systems.

Drug delivery systems (DDSs) are designed to deliver drugs to their specific targets to minimize their toxic effects and improve their susceptibility to clearance during targeted transport. Peptides have high affinity, low immunogenicity, simple amino acid composition, and adjustable molecular size; therefore, most peptides can be coupled to drugs via linkers to form peptide-drug conjugates (PDCs) and act as active pro-drugs. PDCs are widely thought to be promising DDSs, given their ability to improve drug bio-compatibility and physiological stability. Peptide-based DDSs are often used to deliver therapeutic substances such as anti-cancer drugs and nucleic acid-based drugs, which not only slow the degradation rate of drugs in vivo but also ensure the drug concentration at the targeted site and prolong the half-life of drugs in vivo. This article provides an profile of the advancements and future development in functional peptide-based DDSs both domestically and internationally in recent years, in the expectation of achieving targeted drug delivery incorporating functional peptides and taking full advantage of synergistic effects.

SME-MFP: A novel spatiotemporal neural network with multiangle initialization embedding toward multifunctional peptides prediction.

As a promising alternative to conventional antibiotic drugs in the biomedical field, functional peptide has been widely used in disease treatment owing to its low toxicity, high absorption rate, and biological activity. Recently, several machine learning methods have been developed for functional peptide prediction. However, the main research heavily relies on statistical features and few consider multifunctional peptide identification. So, we propose SME-MFP, a novel predictor in the imbalanced multi-label functional peptide datasets. First, we employ physicochemical and evolutionary information to represent the peptide sequence's initialization features from multiple perspectives. Second, the features are fused and then put into spatial feature extractors, where the residual connection and multiscale convolutional neural network extract more discriminative features of different lengths' peptide sequences. Besides, we also design AFT-based temporal feature extractors to fully capture the global interactions of the sequences. Finally, devising a new loss to replace the traditional cross entropy loss to settle the class imbalance problems. The results show that our framework not only enhances the model's ability to capture sequence features effectively, but also accuracy improves by 3.89% over existing methods on public peptide datasets.

Purification, identification and molecular docking of dual-functional peptides derived from corn protein hydrolysates with antioxidant and antiadhesive activity against Helicobacter pylori.

BACKGROUND: More than 50% of the world's population is infected with Helicobacter pylori, which is classified as a group I carcinogen by the World Health Organization (WHO). RESULTS: Corn protein dual-functional peptides were identified and functionally analyzed in vitro and in silico. Two novel dual-functional peptides were identified as Cys-Gln-Asp-Val-Pro-Leu-Leu (CQDVPLL, CQ7) and Thr-Ile-Phe-Pro-Gln-Cys (TIFPQC, TI6) using nanoscale liquid chromatography coupled to tandem mass spectrometry (nano-LC-MS/MS). The antiadhesive effects against H. pylori of CQ7 and TI6 were 45.17 ± 2.41% and 48.62 ± 1.84% at 4 mg mL-1 , respectively. In silico prediction showed that CQ7 and TI6 had good physicochemical properties. Molecular docking demonstrated that CQ7 and TI6 could bind to the adhesins BabA and SabA by hydrophobic interactions and hydrogen bonds, preventing H. pylori infection. Moreover, CQ7 showed strong antioxidant activity due to its unique amino acid composition. CONCLUSION: The present study demonstrated that the identified peptides, CQ7 and TI6, possess antioxidant and antiadhesive effects, preventing H. pylori infection and alleviating oxidative injury to the gastric mucosa. © 2023 Society of Chemical Industry.

Functional Peptide-Modified Liposomes for siRNA Delivery to Rat Retinal Pigment Epithelium Cells: Effect of Peptide Sequences.

Most retinal diseases involve the degeneration of choroidal retinal pigment epithelial (RPE) cells. Because of a blood-retina barrier (tight junction formation), RPE cells restrict the entry of hydrophilic macromolecules (e.g., small interfering RNA (siRNA)) through blood stream and eye drops. A cytoplasm-responsive stearylated (STR) peptide, STR-CH2R4H2C (CH2R4) enables stable siRNA complexation, cell permeation, and intracellular dynamics control. We previously demonstrated how CH2R4-modified liposomes promoted siRNA efficacy. We investigated the influence of amino acid sequences of functional peptides on cellular uptake pathways, siRNA transfection efficacy, and the permeation of peptide-modified liposomes in rat RPE-J cells. Four STR-peptides, consisting of arginine (R), cysteine (C), histidine (H), lysine (K) or serine (S), were designed based on CH2R4. We prepared siRNA-loaded, peptide-modified cationic liposomes (CH2R4-, CH2K4-, CH2S4-, SH2R4-, and SH2S4-lipoplexes). CH2R4-, CH2K4-, and SH2R4-lipoplexes induced cellular uptake by macropinocytosis by activating cytoskeletal F-actin, possibly due to cationic amino acids (arginine, lysine). SH2R4-lipoplexes were trapped in endosomes, whereas CH2R4- and CH2K4-lipoplexes enhanced endosomal siRNA release suggesting cysteine contributes to endosomal escape. Although cationic liposome-based, CH2S4- and SH2S4-lipoplexes (not including arginine and lysine) showed lower siRNA transfection efficiency. This difference may be because siRNAs were retained on both peptide moieties and cationic liposomes in CH2R4-, CH2K4- and SH2R4-lipoplexes, whereas in CH2S4- and SH2S4-lipoplexes, siRNAs were loaded to the cationic liposomes, but not on peptides. In three-dimensional spheroids, CH2R4- and CH2K4-modified liposomes promoted permeation through tight junctions. Thus, cationic amino acids and cysteine within peptide sequences of CH2R4 could be effective for siRNA delivery to the retina using functional peptide-modified liposomes.

A Multifunctional Hybrid Nanocarrier for Non-Invasive siRNA Delivery to the Retina.

Drug therapy for retinal diseases (e.g., age-related macular degeneration, the leading cause of blindness) is generally performed by invasive intravitreal injection because of poor drug delivery caused by the blood-retinal barrier (BRB). This study aimed to develop a nanocarrier for the non-invasive delivery of small interfering RNA (siRNA) to the posterior segment of the eye (i.e., the retina) by eyedrops. To this end, we prepared a hybrid nanocarrier based on a multifunctional peptide and liposomes, and the composition was optimized. A cytoplasm-responsive stearylated peptide (STR-CH2R4H2C) was used as the multifunctional peptide because of its superior ability to enhance the complexation, cell permeation, and intracellular dynamics of siRNA. By adding STR-CH2R4H2C to the surface of liposomes, intracellular uptake increased regardless of the liposome surface charge. The STR-CH2R4H2C-modified cationic nanocarrier demonstrated significant siRNA transfection efficiency with no cytotoxicity, enhanced siRNA release from endosomes, and effectively suppressed vascular endothelial growth factor expression in rat retinal pigment epithelium cells. The 2.0 mol% STR-CH2R4H2C-modified cationic nanocarrier enhanced intraocular migration into the retina after instillation into rat eyes.

Iron Oxide Nanoparticles Decorated with Functional Peptides for a Targeted siRNA Delivery to Glioma Cells.

Glioma is a deadly form of brain cancer, and the difficulty of treating glioma is exacerbated by the chemotherapeutic resistance developed in the tumor cells over the time of treatment. siRNA can be used to silence the gene responsible for the increased resistance, and sensitize the glioma cells to drugs. Here, iron oxide nanoparticles functionalized with peptides (NP-CTX-R10) were used to deliver siRNA to silence O6-methylguanine-DNA methyltransferase (MGMT) to sensitize tumor cells to alkylating drug, Temozolomide (TMZ). The NP-CTX-R10 could complex with siRNA through electrostatic interactions and was able to deliver the siRNA to different glioma cells. The targeting ligand chlorotoxin and cell penetrating peptide polyarginine (R10) enhanced the transfection capability of siRNA to a level comparable to commercially available Lipofectamine. The NP-siRNA was able to achieve up to 90% gene silencing. Glioma cells transfected with NP-siRNA targeting MGMT showed significantly elevated sensitivity to TMZ treatment. This nanoparticle formulation demonstrates the ability to protect siRNA from degradation and to efficiently deliver the siRNA to induce therapeutic gene knockdown.

SNARE Modulators and SNARE Mimetic Peptides.

The soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptor (SNARE) proteins play a central role in most forms of intracellular membrane trafficking, a key process that allows for membrane and biocargo shuffling between multiple compartments within the cell and extracellular environment. The structural organization of SNARE proteins is relatively simple, with several intrinsically disordered and folded elements (e.g., SNARE motif, N-terminal domain, transmembrane region) that interact with other SNAREs, SNARE-regulating proteins and biological membranes. In this review, we discuss recent advances in the development of functional peptides that can modify SNARE-binding interfaces and modulate SNARE function. The ability of the relatively short SNARE motif to assemble spontaneously into stable coiled coil tetrahelical bundles has inspired the development of reduced SNARE-mimetic systems that use peptides for biological membrane fusion and for making large supramolecular protein complexes. We evaluate two such systems, based on peptide-nucleic acids (PNAs) and coiled coil peptides. We also review how the self-assembly of SNARE motifs can be exploited to drive on-demand assembly of complex re-engineered polypeptides.

Functional peptide-mediated plastid transformation in tobacco, rice, and kenaf.

In plant engineering, plastid transformation is more advantageous than nuclear transformation because it results in high levels of protein expression from multiple genome copies per cell and is unaffected by gene silencing. The common plastid transformation methods are biolistic bombardment that requires special instruments and PEG-mediated transformation that is only applicable to protoplast cells. Here, we aimed to establish a new plastid transformation method in tobacco, rice, and kenaf using a biocompatible fusion peptide as a carrier to deliver DNA into plastids. We used a fusion peptide, KH-AtOEP34, comprising a polycationic DNA-binding peptide (KH) and a plastid-targeting peptide (AtOEP34) to successfully deliver and integrate construct DNA into plastid DNA (ptDNA) via homologous recombination. We obtained transformants in each species using selection with spectinomycin/streptomycin and the corresponding resistance gene aadA. The constructs remained in ptDNA for several months after introduction even under non-selective condition. The transformants normally flowered and are fertile in most cases. The offspring of the transformants (the T1 generation) retained the integrated construct DNA in their ptDNA, as indicated by PCR and DNA blotting, and expressed GFP in plastids from the integrated construct DNA. In summary, we successfully used the fusion peptide method for integration of foreign DNA in tobacco, rice, and kenaf ptDNA, and the integrated DNA was transmitted to the next generations. Whereas optimization is necessary to obtain homoplasmic plastid transformants that enable stable heterologous expression of genes, the plastid transformation method shown here is a novel nanomaterial-based approach distinct from the conventional methods, and we propose that this easy method could be used to target a wide variety of plants.

Systemic delivery of siRNA to the colon using peptide modified PEG-PCL polymer micelles for the treatment of ulcerative colitis.

Ulcerative colitis (UC) is a refractory inflammatory bowel disease that causes inflammation and ulcers in the digestive tract, and significantly reduces the patient's quality of life. While existing UC treatments have many challenges, nanotechnology, and small interfering RNA (siRNA) based formulations are novel and promising for UC treatment. We previously reported that intravenous administration of MPEG-PCL-CH2R4H2C nanomicelles had high inflammatory site accumulation and remarkable therapeutic effects on rheumatoid arthritis by a phenomenon similar to enhanced permeability and retention effect. In this study, we investigated the effects of siRNA delivered using MPEG-PCL-CH2R4H2C nanomicelles through intravenous administration to the inflammation site of dextran sulfate sodium-induced colitis mice. The MPEG-PCL-CH2R4H2C micelles had optimum physical properties and high siRNA compaction ability. Moreover, model-siRNA delivered through MPEG-PCL-CH2R4H2C showed higher accumulation in the inflammatory site than that of the naked siRNA. Furthermore, intravenous administration of MPEG-PCL-CH2R4H2C/siRelA micelles, targeting siRelA, a subunit of NF-κB, significantly decreased the shortening of large intestine, clinical score, and production of inflammatory cytokines compared the 5-ASA and naked siRelA. These results suggest that MPEG-PCL-CH2R4H2C is a useful carrier for the systemic delivery and accumulation of siRNA, thus improving its therapeutic effect.

Double-layered adhesive microneedle bandage based on biofunctionalized mussel protein for cardiac tissue regeneration.

Heart failure following myocardial infarction (MI), the primary cause of mortality worldwide, is the consequence of cardiomyocyte death or dysfunction. Clinical efforts involving the delivery of growth factors (GFs) and stem cells with the aim of regenerating cardiomyocytes for the recovery of structural and functional integrity have largely failed to deliver, mainly due to short half-lives and rapid clearance in in vivo environments. In this work, we selected and genetically fused four biofunctional peptides possessing angiogenic potential, originating from extracellular matrix proteins and GFs, to bioengineered mussel adhesive protein (MAP). We found that MAPs fused with vascular endothelial growth factor (VEGF)-derived peptide and fibronectin-derived RGD peptide significantly promoted the proliferation and migration of endothelial cells in vitro. Based on these characteristics, we fabricated advanced double-layered adhesive microneedle bandages (DL-AMNBs) consisting of a biofunctional MAP-based root and a regenerated silk fibroin (SF)-based tip, allowing homogeneous distribution of the regenerative factor via swellable microneedles. Our developed DL-AMNB system clearly demonstrated better preservation of cardiac muscle and regenerative effects on heart remodeling in a rat MI model, which might be attributed to the prolonged retention of therapeutic peptides as well as secure adhesion between the patch and host myocardium by MAP-inherent strong underwater adhesiveness.

A peptide CORO1C-47aa encoded by the circular noncoding RNA circ-0000437 functions as a negative regulator in endometrium tumor angiogenesis.

Circular RNAs (circRNAs) are a novel class of widespread noncoding RNAs that regulate gene expression in mammals. Recent studies demonstrate that functional peptides can be encoded by short open reading frames in noncoding RNAs, including circRNAs. However, the role of circRNAs in various physiological and pathological states, such as cancer, is not well understood. In this study, through deep RNA sequencing on human endometrial cancer (EC) samples and their paired adjacent normal tissues, we uncovered that the circRNA hsa-circ-0000437 is significantly reduced in EC compared with matched paracancerous tissue. The hsa-circ-0000437 contains a short open reading frame encoding a functional peptide termed CORO1C-47aa. Overexpression of CORO1C-47aa is capable of inhibiting angiogenesis at the initiation stage by suppressing endothelial cell proliferation, migration, and differentiation through competition with transcription factor TACC3 to bind to ARNT and suppress VEGF. CORO1C-47aa directly bound to ARNT through the PAS-B domain, and blocking the association between ARNT and TACC3, which led to reduced expression of VEGF, ultimately lead to reduced angiogenesis. The antitumor effects of CORO1C-47aa on EC progression suggest that CORO1C-47aa has potential value in anticarcinoma therapies and warrants further investigation.

Intracellular Paclitaxel Delivery Facilitated by a Dual-Functional CPP with a Hydrophobic Hairpin Tail.

In our pervious study, a dual-functional peptide R7 was developed to form a complex with paclitaxel (PTX) for enhancement of PTX translocation. However, because of the unstable noncovalent bond between R7 and PTX, PTX redistributed after the introduction of heparin, leading to R7-PTX complex dissociation, further causing less PTX penetration than expected. Thus, a novel positive CPP carrier of P9 was developed to improve CPP-PTX affinity via a double-proline (Pro, P) hairpin tail and enhance PTX translocation through the reduction of translocation energy barrier, confirmed by the MM-PBSA analysis and umbrella sampling simulation. Cellular uptake study reveals that P9 can quickly translocate into the HeLa cells within 1 min and exhibits no noticeable cytotoxicity. Compared to R7, P9 is able to help PTX translocation, leading to a remarkable increase in the intracellular concentration of PTX, eventually resulting in a significant loss in tumor cell viability. In vivo experiments demonstrate that a vein injection of P9-PTX complex dramatically inhibits tumor growth. Our study provides a novel perspective for designing CPP-facilitated drug carrier to enhance antitumor efficiency.

An effective datasets describing antimicrobial peptide produced from Pediococcus acidilactici - purification and mode of action determined by molecular docking.

Most of the probiotics Bacterial cells, express native antibacterial genes, resulting in the production of, antimicrobial peptides, which have various applications in biotechnology and drug development. But the identification of antibacterial peptide, structural characterization of antimicrobial peptide and prediction on mode of action. Regardless of the significance of protein manufacturing, three individual factors are required for the production method: gene expression, stabilization and specific peptide purification. Our protocol describes a straightforward technique of detecting and characterizing particular extracellular peptides and enhancing the antimicrobial peptide expression we optimized using low molecular weight peptides. This protocol can be used to improve peptide detection and expression. The following are the benefits of this method, (DOI - https://doi.org/10.1016/j.ijbiomac.2019.10.196 [1]). The data briefly describe a simple method in detection identification, characterization of antimicrobial extracellular peptide, predicating the mode of action of peptide in targeting pathogens (In-silico method), brief method on profiling of antimicrobial peptide and its mode of action [1]. Further the protocol can be used to enhance the specific peptide expressions, detection of peptides. The advantages of this technique are presented below:•Characterization protocol of specific antimicrobial peptide•The folded antimicrobial peptide expression were less expressed or non-expressed peptides.•Besides being low cost, less time-consuming, easy to handle, universal and fast to execute, the suggested technique can be used for multiple proteins expressed in probiotics (Lactobacillus species) expression system.

Designed antifouling peptides planted in conducting polymers through controlled partial doping for electrochemical detection of biomarkers in human serum.

An antifouling electrochemical biosensing platform was constructed based on conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) planted with designed peptides. The designed peptides containing doping and antifouling sequences were anchored to an electrode surface, followed by the electrochemical polymerization of PEDOT. The negatively charged doping sequence of the peptide was gradually doped into the PEDOT during the polymerization process, and by controlling the polymerization time, it was able to exactly dope the whole doping sequence into the PEDOT film, leaving the antifouling sequence of the peptide stretched out of the PEDOT surface. Therefore, an excellent conducting and antifouling platform was constructed just like planting a peptide tree in the PEDOT soil. With antibodies immobilized on the peptide, an antifouling electrochemical biosensor for the detection of a typical biomarker CA15-3 was developed. Owing to the unique properties of the conducting polymer PEDOT and the antifouling peptide, the electrochemical biosensor exhibited high sensitivity and long-term stability, and it was capable of detecting CA15-3 in serum of breast cancer patients without suffering from biofouling. The strategy of planting designed antifouling peptides in conducting polymers offered an effective way to develop electrochemical sensors for practical biomarkers assaying in complex biological samples.

Functional potato bioactive peptide intensifies Nrf2-dependent antioxidant defense against renal damage in hypertensive rats.

Hypertension, which is known as a silent killer, is the second leading cause of kidney failure worldwide. Elevated blood pressure causes approximately 7.6 million deaths, which account for ~13.5% of the total deaths and will continue to rise. High blood pressure is the prime risk factor associated with complications in major organs, including the heart, brain and kidney. High blood pressure accelerates oxidative stress and thereby causes organ dysfunction through the production of reactive oxygen species. In this study, we investigated the renal-protective effects of the bioactive peptide IF from alcalase potato protein hydrolysate in spontaneously hypertensive rat kidney. Sixteen-week-old spontaneously hypertensive rats were divided into three groups (n = 6), and Sixteen-week-old Wistar Kyoto rats (n = 6) served as the control group. The rats were administered IF and captopril via oral gavage for 8 weeks and then sacrificed, and their kidneys were harvested. The kidney sections from the rats treated with IF showed restoration of the structure of the glomerulus and Bowman's capsule. The expression levels of Nrf2-mediated antioxidants were also increased, as confirmed by 4-hydroxynonenal immunohistochemical staining. The TUNEL assay revealed a significant reduction in the number of apoptotic cells in the IF-treated groups, which was consistent with the western blot results. Thus, the bioactive peptide IF exerts potential protective effects against hypertension-associated ROS-mediated renal damage via the Nrf2-dependent antioxidant pathway along the DJ-1 and AKT axes. Hence, we speculate that IF might have promising therapeutic effects on renal damage associated with hypertension.

Anti-Metastatic Effects on Melanoma via Intravenous Administration of Anti-NF-κB siRNA Complexed with Functional Peptide-Modified Nano-Micelles.

Controlling metastasis is an important strategy in cancer treatment. Nanotechnology and nucleic acids with novel modalities are promising regulators of cancer metastasis. We aimed to develop a small interfering RNA (siRNA) systemic delivery and anti-metastasis system using nanotechnology. We previously reported that polyethylene glycol-polycaprolactone (PEG-PCL) and functional peptide CH2R4H2C nano-micelle (MPEG-PCL-CH2R4H2C) has high siRNA silencing effects, indicated by increased drug accumulation in tumor-bearing mice, and has an anti-tumor effect on solid tumors upon systemic injection. In this study, we aimed to apply our micelles to inhibit metastasis and evaluated the inhibitory effect of anti-RelA siRNA (siRelA), which is a subunit of NF-κB conjugated with MPEG-PCL-CH2R4H2C, via systemic administration. We report that siRelA/MPEG-PCL-CH2R4H2C had a high cellular uptake and suppressed the migration/invasion of cells in B16F10 cells without toxicity. In addition, in a lung metastasis mouse model using intravenous administration of B16F10 cells treated with siRelA/MPEG-PCL-CH2R4H2C, the number of lung nodules in lung tissue significantly decreased compared to naked siRelA and siControl/MPEG-PCL-CH2R4H2C micelle treatments. Hence, we show that RelA expression can reduce cancer metastasis, and MPEG-PCL-CH2R4H2C is an effective siRNA carrier for anti-metastasis cancer therapies.

Novel Bi-Functional 14-mer Peptides with Both Ovarian Carcinoma Cells Targeting and Magnetic Fe3O4Nanoparticles Affinity.

Fe3O4 magnetic nanoparticles (Fe3O4-MNPs) have attracted much interest for their potential medical applications due to their desirable magnetic properties. However, their potential cytotoxicity, high RES clearance in circulation, and nonspecific distribution in tissue might be the main obstacles in practice. In the present study, a novel bi-functional 14-mer peptide with both ovarian carcinoma cells targeting and magnetic Fe3O4 nanoparticles affinity was designed and synthesized, and then a facile and effective modification method was developed to bestow the Fe3O4-MNPs with tumor-targeting capability via modification, using the bi-functional peptides. First, on the basis of a tumor-targeting 7-mer peptide QQTNWSL (Q-L) and another Fe3O4-MNPs-targeting 7-mer peptide TVNFKLY (T-Y)-screened by phage-displayed peptide libraries-two bi-functional 14-mer peptides sequenced as LSWNTQQ-YLKFNVT (abbreviated as LQ-YT) and QQTNWSL-YLKFNVT (QL-YT) were synthesized through combining the Q-L peptide and T-Y peptide in predetermined configurations. Their specificity for bonding with A2780 tumor cells and affinity for Fe3O4-MNPs were verified. Then the bi-functional 14-mer peptides were applied to modify the Fe3O4-MNPs. Results showed that both bi-functional 14-mer peptides could be conjugated to the Fe3O4-MNPs surface with high affinity. Immunofluorescence and Prussian blue staining assays indicated that the LQ-YT-modified Fe3O4-MNPs could specifically bond to A2780 tumor cells. In addition to our findings suggesting that more ß-turns and random coils are conducive to increasing polypeptide surface area for binding and exposing the target group and bonding sites on LQ-YT to external targets, we demonstrated that the bi-functional 14-mer peptide has affinity for Fe3O4-MNPs, and that Fe3O4-MNPs, which was modified with a 14-mer peptide, could be bestowed with a targeting affinity for ovarian carcinoma cells.

Cleavage of the Babuvirus Movement Protein B4 into Functional Peptides Capable of Host Factor Conjugation is Required for Virulence.

Banana bunchy top virus (BBTV) poses a serious danger to banana crops worldwide. BBTV-encoded protein B4 is a determinant of pathogenicity. However, the relevant molecular mechanisms underlying its effects remain unknown. In this study, we found that a functional peptide could be liberated from protein B4, likely via proteolytic processing. Site-directed mutagenesis indicated that the functional processing of protein B4 is required for its pathogenic effects, including dwarfism and sterility, in plants. The released protein fragment targets host proteins, such as the large subunit of RuBisCO (RbcL) and elongation factor 2 (EF2), involved in protein synthesis. Therefore, the peptide released from B4 (also a precursor) may act as a non-canonical modifier to influence host-pathogen interactions involving BBTV and plants.

Antimicrobial peptide similarity and classification through rough set theory using physicochemical boundaries.

BACKGROUND: Antimicrobial peptides attract considerable interest as novel agents to combat infections. Their long-time potency across bacteria, viruses and fungi as part of diverse innate immune systems offers a solution to overcome the rising concerns from antibiotic resistance. With the rapid increase of antimicrobial peptides reported in the databases, peptide selection becomes a challenge. We propose similarity analyses to describe key properties that distinguish between active and non-active peptide sequences building upon the physicochemical properties of antimicrobial peptides. We used an iterative supervised machine learning approach to classify active peptides from inactive peptides with low false discovery rates in a relatively short computational search time. RESULTS: By generating explicit boundaries, our method defines new categories of active and inactive peptides based on their physicochemical properties. Consequently, it describes physicochemical characteristics of similarity among active peptides and the physicochemical boundaries between active and inactive peptides in a single process. To build the similarity boundaries, we used the rough set theory approach; to our knowledge, this is the first time that this approach has been used to classify peptides. The modified rough set theory method limits the number of values describing a boundary to a user-defined limit. Our method is optimized for specificity over selectivity. Noting that false positives increase activity assays while false negatives only increase computational search time, our method provided a low false discovery rate. Published datasets were used to compare our rough set theory method to other published classification methods and based on this comparison, we achieved high selectivity and comparable sensitivity to currently available methods. CONCLUSIONS: We developed rule sets that define physicochemical boundaries which allow us to directly classify the active sequences from inactive peptides. Existing classification methods are either sequence-order insensitive or length-dependent, whereas our method generates the rule sets that combine order-sensitive descriptors with length-independent descriptors. The method provides comparable or improved performance to currently available methods. Discovering the boundaries of physicochemical properties may lead to a new understanding of peptide similarity.