Journal of Peptide Science最新文献

{"title":"Antiviral peptides inhibiting the main protease of SARS-CoV-2 investigated by computational screening and in vitro protease assay","authors":"James Stewart,&nbsp;Jakaria Shawon,&nbsp;Md Ackas Ali,&nbsp;Blaise Williams,&nbsp;A. D. A. Shahinuzzaman,&nbsp;Sharmin Akther Rupa,&nbsp;Taha Al-Adhami,&nbsp;Ruoqing Jia,&nbsp;Cole Bourque,&nbsp;Ryan Faddis,&nbsp;Kaylee Stone,&nbsp;Md Abu Sufian,&nbsp;Rajib Islam,&nbsp;Andrew C. McShan,&nbsp;Khondaker Miraz Rahman,&nbsp;Mohammad A. Halim","doi":"10.1002/psc.3553","DOIUrl":"10.1002/psc.3553","url":null,"abstract":"<p>The main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays an important role in viral replication and transcription and received great attention as a vital target for drug/peptide development. Therapeutic agents such as small-molecule drugs or peptides that interact with the Cys–His present in the catalytic site of Mpro are an efficient way to inhibit the protease. Although several emergency-approved vaccines showed good efficacy and drastically dropped the infection rate, evolving variants are still infecting and killing millions of people globally. While a small-molecule drug (Paxlovid) received emergency approval, small-molecule drugs have low target specificity and higher toxicity. Besides small-molecule drugs, peptide therapeutics are thus gaining increasing popularity as they are easy to synthesize and highly selective and have limited side effects. In this study, we investigated the therapeutic value of 67 peptides targeting Mpro using molecular docking. Subsequently, molecular dynamics (MD) simulations were implemented on eight protein–peptide complexes to obtain molecular-level information on the interaction between these peptides and the Mpro active site, which revealed that temporin L, indolicidin, and lymphocytic choriomeningitis virus (LCMV) GP1 are the best candidates in terms of stability, interaction, and structural compactness. These peptides were synthesized using the solid-phase peptide synthesis protocol, purified by reversed-phase high-performance liquid chromatography (RP-HPLC), and authenticated by mass spectrometry (MS). The in vitro fluorometric Mpro activity assay was used to validate the computational results, where temporin L and indolicidin were observed to be very active against SARS-CoV-2 Mpro with IC₅₀ values of 38.80 and 87.23 μM, respectively. A liquid chromatography–MS (LC–MS) assay was developed, and the IC₅₀ value of temporin L was measured at 23.8 μM. The solution-state nuclear magnetic resonance (NMR) structure of temporin L was determined in the absence of sodium dodecyl sulfate (SDS) micelles and was compared to previous temporin structures. This combined investigation provides critical insights and assists us to further develop peptide inhibitors of SARS-CoV-2 Mpro through structural guided investigation.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138460614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cysteine-free cone snail venom peptides: Classification of precursor proteins and identification of mature peptides","authors":"Marimuthu Vijayasarathy,&nbsp;Sanjeev Kumar,&nbsp;Rajdeep Das,&nbsp;Padmanabhan Balaram","doi":"10.1002/psc.3554","DOIUrl":"10.1002/psc.3554","url":null,"abstract":"<p>The cysteine-free acyclic peptides present in marine cone snail venom have been much less investigated than their disulfide bonded counterparts. Precursor protein sequences derived from transcriptomic data, together with mass spectrometric fragmentation patterns for peptides present in venom duct tissue extracts, permit the identification of mature peptides. Twelve distinct gene superfamiles have been identified with precursor lengths between 64 and 158 residues. In the case of <i>Conus monile</i>, three distinct mature peptides have been identified, arising from two distinct protein precursors. Mature acyclic peptides are often post-translationally modified, with C-terminus amidation, a feature characteristic of neuropeptides. In the present study, 20 acyclic peptides from <i>Conus monile</i> and <i>Conus betulinus</i> were identified. The common modifications of C-terminus amidation, gamma carboxylation of glutamic acid (E to ϒ), N-terminus conversion of Gln (Q) to a pyroglutamyl residue (Z), and hydroxylation of Pro (P) to Hyp (O) are observed in one or more peptides identified in this study. Proteolytic trimming of sequences by cleavage at the C-terminus of Asn (N) residues is established. The presence of an asparagine endopeptidase is strengthened by the identification of legumain-like sequences in the transcriptome assemblies from diverse <i>Conus</i> species. Such sequences may be expected to have a cleavage specificity at Asn-Xxx peptide bonds.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ernesto Scoffone: A great scientist, colleague, and mentor","authors":"Claudio Toniolo,&nbsp;Marta De Zotti","doi":"10.1002/psc.3552","DOIUrl":"10.1002/psc.3552","url":null,"abstract":"","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71482785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring biocompatible chemistry to create stapled and photoswitchable variants of the antimicrobial peptide aurein 1.2","authors":"Alexandra E. Coram,&nbsp;Richard Morewood,&nbsp;Saan Voss,&nbsp;Joshua L. Price,&nbsp;Christoph Nitsche","doi":"10.1002/psc.3551","DOIUrl":"10.1002/psc.3551","url":null,"abstract":"<p>Antibiotic resistance is an escalating global health threat. Due to their diverse mechanisms of action and evasion of traditional resistance mechanisms, peptides hold promise as future antibiotics. Their ability to disrupt bacterial membranes presents a potential strategy to combat drug-resistant infections and address the increasing need for effective antimicrobial treatments. Amphipathic α-helical peptides possess a distinctive molecular structure with both charged/hydrophilic and hydrophobic regions that interact with the bacterial cell membrane, disrupting its structural integrity. The α-helical amphipathic peptide aurein 1.2, secreted by the Australian frog <i>Litoria aurea</i>, is one of the shortest known antimicrobial peptides, spanning only 13 amino acids. The primary objective of this study was to investigate stapled and photoswitchable modifications of short helical peptides employing biocompatible chemistry, utilising aurein 1.2 as a model system. We developed various stapled versions of aurein 1.2 using biocompatible conjugation chemistry between dicyanopyridine and 1,2-aminothiols. While the commonly employed stapling pattern for longer staples is <i>i</i>, <i>i</i> + 7, we observed superior helicity in peptides stapled at positions <i>i</i>, <i>i</i> + 8. Molecular dynamics simulations confirmed both stapling patterns to support an α-helical peptide conformation. Additionally, we utilised a cysteine-selective photosensitive staple, perfluoro azobenzene, to explore photoswitchable variants of aurein 1.2. A double-cysteine variant stapled at <i>i</i>, <i>i</i> + 7 indeed exhibited a change in overall helicity induced by light. We further demonstrated the applicability of this staple to attach to cysteine residues in <i>i</i>, <i>i</i> + 7 positions of a helix in a model protein. While some of the stapled variants displayed substantial increase in helicity, minimal inhibitory concentration assays revealed that none of the stapled aurein 1.2 variants exhibited increased antimicrobial activity compared to the wildtype.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/psc.3551","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71482786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibacterial and in vitro anticancer activities of the antimicrobial peptide NRC-07 encapsulated in chitosan nanoparticles","authors":"Nancy O. Turky,&nbsp;Noura A. Abdelmonem,&nbsp;Salma N. Tammam,&nbsp;Mohamed Z. Gad,&nbsp;Hans-Georg Breitinger,&nbsp;Ulrike Breitinger","doi":"10.1002/psc.3550","DOIUrl":"10.1002/psc.3550","url":null,"abstract":"<p>Antimicrobial peptides (AMPs) are promising alternatives to conventional antibiotics and chemotherapy in the treatment of multidrug-resistant pathogens and drug-resistant cancers. Clinical application of AMPs is limited due to low stability and inefficient transport. Encapsulation in nanocarriers may improve their therapeutic potential. Chitosan nanoparticles (CS-NPs) are efficient carriers for proteins and peptides, improving the treatment of microbial infections and targeted drug delivery. We examined toxicity against cancer cell lines and antibacterial activities of the pleurocidin-like AMP NRC-07 upon encapsulation in CS-NPs by ionotropic gelation. The biological activities of various formulations of free and encapsulated NRC-07 and free nanoparticles were evaluated against <i>Pseudomonas aeruginosa</i> and breast cancer cells, using assays for cell viability and lactate dehydrogenase cytolysis with non-cancer cell lines as controls. NRC-07-containing nanoparticles decreased the bacterial and cancer cell viability in a concentration-dependent manner. Activities of encapsulated peptide were &gt;2-fold higher than those of free NRC-07 peptide. Unloaded CS-NPs and free peptide were not cytotoxic against control cells. Encapsulation of NRC-07 into CS-NPs enhanced the antibacterial and selective cytotoxicity of the peptide, possibly enhancing anticancer activities. Encapsulation presents a promising tool for the development of efficient drug delivery systems.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49678788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in heavy metal binding to cysteine-containing coiled-coil peptides","authors":"Prianka Luther,&nbsp;Aimee L. Boyle","doi":"10.1002/psc.3549","DOIUrl":"10.1002/psc.3549","url":null,"abstract":"<p>One third of all structurally characterised proteins contain a metal; however, the interplay between metal-binding and peptide/protein folding has yet to be fully elucidated. To better understand how metal binding affects peptide folding, a range of metals should be studied within a specific scaffold. To this end, we modified a histidine-containing coiled-coil peptide to create a cysteine-containing scaffold, named CX3C, which was designed to bind heavy metal ions. In addition, we generated a peptide named CX2C, which contains a binding site more commonly found in natural proteins. Using a combination of analytical techniques including circular dichroism (CD) spectroscopy, UV–Vis spectroscopy and size-exclusion chromatography coupled to multi-angle light scattering (SEC-MALS), we examined the differences in the metal-binding properties of the two peptides. Both peptides are largely unfolded in the apo state due to the disruption of the hydrophobic core by inclusion of the polar cysteine residues. However, this unfolding is overcome by the addition of Cd(II), Pb(II) and Hg(II), and helical assemblies are formed. Both peptides have differing affinities for these metal ions, a fact likely attributed to the differing sizes of the ions. We also show that the oligomerisation state of the peptide complexes and the coordination geometries of the metal ions differ between the two peptide scaffolds. These findings highlight that subtle changes in the primary structure of a peptide can have considerable implications for metal binding.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/psc.3549","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41203840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid, traceless and facile peptide cyclization enabled by tetrazine-thiol exchange","authors":"Daniëlle W. T. Geers,&nbsp;Katerina Gavriel,&nbsp;Kevin Neumann","doi":"10.1002/psc.3548","DOIUrl":"10.1002/psc.3548","url":null,"abstract":"<p>Cyclic peptides offer many advantages compared to their linear counterparts, including prolonged stability within the biological environment and enhanced binding affinity. Typically, peptides are cyclized by forming an amide bond, either on-resin or in solution, through extensive use of orthogonal protecting groups or chemoselective ligation strategies, respectively. Here, we show that the chemoselective tetrazine-thiol exchange is a powerful tool for rapid <i>in situ</i> cyclization of peptides without the need for additional activation reagents or extensive protecting group reshuffling. The reaction between N-terminal sulfide-bearing unsymmetric tetrazines and internal cysteines occurs spontaneously within a mildly acidic environment (pH 6.5) and is of traceless nature. The rapidly available unsymmetric sulfide tetrazine building blocks can be incorporated on resin using standard solid-phase peptide synthesis protocols and are orthogonal to trifluoroacetic acid cleavage conditions. The cyclized peptides display high stability, even when incubated with a large excess of free thiols. Due to its traceless and mild nature, we expect that the tetrazine-thiol exchange will be of high value for the <i>in situ</i> formation of cyclic peptide libraries, thus being applicable in drug discovery and development.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/psc.3548","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41136203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of the modification of the cosmetic peptide Argireline on the affinity toward copper(II) ions","authors":"Dariusz Wyrzykowski,&nbsp;Robert Wieczorek,&nbsp;Anna Kloska,&nbsp;Fosca Errante,&nbsp;Anna Maria Papini,&nbsp;Joanna Makowska","doi":"10.1002/psc.3547","DOIUrl":"10.1002/psc.3547","url":null,"abstract":"<p>Argireline (Ac-EEMQRR-NH₂), a well-known neurotransmitter peptide with a potency similar to botulinum neurotoxins, reveals a proven affinity toward Cu(II) ions. We report herein Cu(II) chelating properties of three new Argireline derivatives, namely, AN4 (Ac-EAHRR-NH₂), AN5 (Ac-EEHQRR-NH₂), and AN6 (Ac-EAHQRK-NH₂). Two complementary experimental techniques, i.e., potentiometric titration (PT) and isothermal titration calorimetry (ITC), have been employed to describe the acid–base properties of the investigated peptides as well as the thermodynamic parameters of the Cu(II) complex formation. Additionally, based on density functional theory (DFT) calculations, we propose the most likely structures of the resulting Cu-peptide complexes. Finally, the cytotoxicity of the free peptides and the corresponding Cu(II) complexes was estimated in human skin cells for their possible future cosmetic application. The biological results were subsequently compared with free Argireline, its Cu(II)-complexes, and the previously studied AN2 derivative (EAHQRR).</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41120724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upgrading of the general AMBER force field 2 for fluorinated alcohol biosolvents: A validation for water solutions and melittin solvation","authors":"Michele Casoria,&nbsp;Marina Macchiagodena,&nbsp;Paolo Rovero,&nbsp;Claudia Andreini,&nbsp;Anna Maria Papini,&nbsp;Gianni Cardini,&nbsp;Marco Pagliai","doi":"10.1002/psc.3543","DOIUrl":"10.1002/psc.3543","url":null,"abstract":"<p>The standard GAFF2 force field parameterization has been refined for the fluorinated alcohols 2,2,2-trifluoroethanol (TFE), 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), and 1,1,1,3,3,3-hexafluoropropan-2-one (HFA), which are commonly used to study proteins and peptides in biomimetic media. The structural and dynamic properties of both proteins and peptides are significantly influenced by the biomimetic environment created by the presence of these cosolvents in aqueous solutions. Quantum mechanical calculations on stable conformers were used to parameterize the atomic charges. Different systems, such as pure liquids, aqueous solutions, and systems formed by melittin protein and cosolvent/water solutions, have been used to validate the new models. The calculated macroscopic and structural properties are in agreement with experimental findings, supporting the validity of the newly proposed models.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/psc.3543","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41119031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in MRI: Peptide and peptidomimetic-based contrast agents","authors":"Giovanni Pierri,&nbsp;Rosaria Schettini","doi":"10.1002/psc.3544","DOIUrl":"10.1002/psc.3544","url":null,"abstract":"<p>Magnetic resonance imaging (MRI) is a common medical imaging technique that provides three-dimensional body images. MRI contrast agents improve image contrast by raising the rate of water proton relaxation in specific tissues. Peptides and peptidomimetics act as scaffolds for MRI imaging agents because of their increased size and offer the possibility to engine a higher hydration value within the design. The design of a new Gd-based contrast agent must take into account high stability constants to avoid free Gd(III), with the subsequent nephrotoxicity, and high relaxivity values. This review analyzes various synthetic approaches, reports studies of relaxometric parameters, and focuses on the description and application of Gd(III)-chelates based on peptide and peptidomimetic scaffolds. In addition, the X-ray molecular structures of three DOTA complexes will be reported to emphasize the necessity of using the X-ray diffraction analysis to identify the coordination sphere of the metals and the mechanism of action of the compounds.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/psc.3544","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41164623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}