Journal of Peptide Science最新文献_第10页

Recent progress in the reprogramming of nonribosomal peptide synthetases 非核糖体肽合成酶重编程的最新进展。

IF 2.1 4区生物学

Journal of Peptide Science Pub Date : 2023-09-18 DOI: 10.1002/psc.3545

Fumihiro Ishikawa, Shinya Nakamura, Isao Nakanishi, Genzoh Tanabe

引用次数: 0

Modular synthetic strategy for N/C-terminal protected amyloidogenic peptides N/C 端受保护淀粉样蛋白生成肽的模块化合成策略。

IF 2.1 4区生物学

Journal of Peptide Science Pub Date : 2023-09-13 DOI: 10.1002/psc.3546

Taka Sawazaki, Youhei Sohma

引用次数: 0

Chemically modified antiviral peptides against SARS-CoV-2 针对 SARS-CoV-2 的化学修饰抗病毒肽。

IF 2.1 4区生物学

Journal of Peptide Science Pub Date : 2023-09-12 DOI: 10.1002/psc.3541

Michael Quagliata, Anna Maria Papini, Paolo Rovero

{"title":"Chemically modified antiviral peptides against SARS-CoV-2","authors":"Michael Quagliata, Anna Maria Papini, Paolo Rovero","doi":"10.1002/psc.3541","DOIUrl":"10.1002/psc.3541","url":null,"abstract":"To date, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) COVID-19 pandemic continues to be a potentially lethal disease. Although both vaccines and specific antiviral drugs have been approved, the search for more specific therapeutic approaches is still ongoing. The infection mechanism of SARS-CoV-2 consists of several stages, and each one can be selectively blocked to disrupt viral infection. Peptides are a promising class of antiviral compounds, which may be suitably modified to be more stable, more effective, and more selective towards a specific viral replication step. The latter two goals might be obtained by increasing the specificity and/or the affinity of the interaction with a specific target and often imply the stabilization of the secondary structure of the active peptide. This review is focused on modified antiviral peptides against SARS-CoV-2 acting at different stages of virus replication, including ACE2-RBD interaction, membrane fusion mechanism, and the proteolytic cleavage by different viral proteases. Therefore, the landscape presented herein provides a useful springboard for the design of new and powerful antiviral therapeutics.","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/psc.3541","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10278102","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}

引用次数: 0

Semisynthesis of A6–A11 lactam insulin A6-A11 内酰胺胰岛素的半合成。

IF 2.1 4区生物学

Journal of Peptide Science Pub Date : 2023-09-11 DOI: 10.1002/psc.3542

Rong Xu, Edwina Jap, Ben Gubbins, Christoph E. Hagemeyer, John A. Karas

{"title":"Semisynthesis of A6–A11 lactam insulin","authors":"Rong Xu, Edwina Jap, Ben Gubbins, Christoph E. Hagemeyer, John A. Karas","doi":"10.1002/psc.3542","DOIUrl":"10.1002/psc.3542","url":null,"abstract":"Insulin replacement therapy is essential for the management of diabetes. However, despite the relative success of this therapeutic strategy, there is still a need to improve glycaemic control and the overall quality of life of patients. This need has driven research into orally available, glucose-responsive and rapid-acting insulins. A key consideration during analogue development is formulation stability, which can be improved via the replacement of insulin's A6–A11 disulfide bond with stable mimetics. Unfortunately, analogues such as these require extensive chemical synthesis to incorporate the nonnative cross-links, which is not a scalable synthetic approach. To address this issue, we demonstrate proof of principle for the semisynthesis of insulin analogues bearing nonnative A6–A11 cystine isosteres. The key feature of our synthetic strategy involves the use of several biosynthetically derived peptide precursors which can be produced at scale cost-effectively and a small, chemically synthesised A6–A11 macrocyclic lactam fragment. Although the assembled A6–A11 lactam insulin possesses poor biological activity in vitro, our synthetic strategy can be applied to other disulfide mimetics that have been shown to improve thermal stability without significantly affecting activity and structure. Moreover, we envisage that this new semisynthetic approach will underpin a new generation of hyperstable proteomimetics.","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/psc.3542","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10211150","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}

引用次数: 0

Interhelical E@g-N@a interactions modulate coiled coil stability within a de novo set of orthogonal peptide heterodimers 螺旋间 E@g-N@a 相互作用可调节一组新的正交肽异二聚体的盘绕稳定性。

IF 2.1 4区生物学

Journal of Peptide Science Pub Date : 2023-09-10 DOI: 10.1002/psc.3540

Anthony R. Perez, Yumie Lee, Michael E. Colvin, Andrea D. Merg

{"title":"Interhelical E@g-N@a interactions modulate coiled coil stability within a de novo set of orthogonal peptide heterodimers","authors":"Anthony R. Perez, Yumie Lee, Michael E. Colvin, Andrea D. Merg","doi":"10.1002/psc.3540","DOIUrl":"10.1002/psc.3540","url":null,"abstract":"The designability of orthogonal coiled coil (CC) dimers, which draw on well-established design rules, plays a pivotal role in fueling the development of CCs as synthetically versatile assembly-directing motifs for the fabrication of bionanomaterials. Here, we aim to expand the synthetic CC toolkit through establishing a “minimalistic” set of orthogonal, de novo CC peptides that comprise 3.5 heptads in length and a single buried Asn to prescribe dimer formation. The designed sequences display excellent partner fidelity, confirmed via circular dichroism (CD) spectroscopy and Ni-NTA binding assays, and are corroborated in silico using molecular dynamics (MD) simulation. Detailed analysis of the MD conformational data highlights the importance of interhelical E@g-N@a interactions in coordinating an extensive 6-residue hydrogen bonding network that “locks” the interchain Asn-Asn′ contact in place. The enhanced stability imparted to the Asn-Asn′ bond elicits an increase in thermal stability of CCs up to ~15°C and accounts for significant differences in stability within the collection of similarly designed orthogonal CC pairs. The presented work underlines the utility of MD simulation as a tool for constructing de novo, orthogonal CCs, and presents an alternative handle for modulating the stability of orthogonal CCs via tuning the number of interhelical E@g-N@a contacts. Expansion of CC design rules is a key ingredient for guiding the design and assembly of more complex, intricate CC-based architectures for tackling a variety of challenges within the fields of nanomedicine and bionanotechnology.","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/psc.3540","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10201712","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}

引用次数: 0

Morpholine, a strong contender for Fmoc removal in solid-phase peptide synthesis 吗啉，固相肽合成中去除 Fmoc 的有力竞争者。

IF 2.1 4区生物学

Journal of Peptide Science Pub Date : 2023-08-23 DOI: 10.1002/psc.3538

Sinenhlanhla N. Mthembu, Amit Chakraborty, Ralph Schönleber, Fernando Albericio, Beatriz G. de la Torre

引用次数: 0

Selection of collagen IV fragments forming the outer sphere of the native protein: Assessment of biological activity for regenerative medicine 挑选形成原生蛋白外层的胶原蛋白 IV 片段：评估再生医学的生物活性。

IF 2.1 4区生物学

Journal of Peptide Science Pub Date : 2023-08-22 DOI: 10.1002/psc.3537

Angelika Becht, Justyna Frączyk, Joanna Waśko, Elżbieta Menaszek, Jakub Kajdanek, Katarzyna Miłowska, Beata Kolesinska

{"title":"Selection of collagen IV fragments forming the outer sphere of the native protein: Assessment of biological activity for regenerative medicine","authors":"Angelika Becht, Justyna Frączyk, Joanna Waśko, Elżbieta Menaszek, Jakub Kajdanek, Katarzyna Miłowska, Beata Kolesinska","doi":"10.1002/psc.3537","DOIUrl":"10.1002/psc.3537","url":null,"abstract":"The aim of this research was to select the fragments that make up the outer layer of the collagen IV (COL4A6) protein and to assess their potential usefulness for regenerative medicine. It was expected that because protein–protein interactions take place via contact between external domains, the set of peptides forming the outer sphere of collagen IV will determine its interaction with other proteins. Cellulose-immobilized protein fragment libraries treated with polyclonal anti-collagen IV antibodies were used to select the peptides forming the outer sphere of collagen IV. In the first test, 33 peptides that strongly interacted with the polyclonal anti-collagen IV antibodies were selected from a library of non-overlapping fragments of collagen IV. The selected fragments of collagen IV (cleaved from the cellulose matrix) were tested for their cytotoxicity, their effects on cell viability and proliferation, and their impact on the formation of reactive oxygen species (ROS). The studies used RAW 264.7 mouse macrophage cells and Hs 680.Tr human fibroblasts. PrestoBlue, ToxiLight™, and ToxiLight 100% Lysis Control assays were conducted. The viability of fibroblasts cultured with the addition of increasing concentrations of the peptide mix did not show statistically significant differences from the control. Fragments 161–170, 221–230, 721–730, 1331–1340, 1521–1530, and 1661–1670 of COL4A6 were examined for cytotoxicity against BJ normal human foreskin fibroblasts. None of the collagen fragments were found to be cytotoxic. Further research is underway on the potential uses of collagen IV fragments in regenerative medicine.","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10053754","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}

引用次数: 0

The development and optimisation of an HPLC-based in vitro serum stability assay for a calcitonin gene-related peptide receptor antagonist peptide 开发并优化基于高效液相色谱法的降钙素基因相关肽受体拮抗剂肽体外血清稳定性检测方法。

IF 2.1 4区生物学

Journal of Peptide Science Pub Date : 2023-08-21 DOI: 10.1002/psc.3539

Vera D'Aloisio, Adam Schofield, David A. Kendall, Gillian A. Hutcheon, Christopher R. Coxon

{"title":"The development and optimisation of an HPLC-based in vitro serum stability assay for a calcitonin gene-related peptide receptor antagonist peptide","authors":"Vera D'Aloisio, Adam Schofield, David A. Kendall, Gillian A. Hutcheon, Christopher R. Coxon","doi":"10.1002/psc.3539","DOIUrl":"10.1002/psc.3539","url":null,"abstract":"Evaluation of the stability of peptide drug candidates in biological fluids, such as blood serum, is of high importance during the lead optimisation phase. Here, we describe the optimisation and validation of a method for the evaluation of the stability of a lead calcitonin gene-related peptide antagonist peptide (P006) in blood serum. After initially determining appropriate peptide and human serum concentrations and selection of the quenching reagent, the HPLC method optimisation used two experimental designs, Plackett–Burman design and Taguchi design. The analytical method was validated as complying with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines. The optimised method allowed the successful resolution of the parent peptide from its metabolites using RP-HPLC and identification of the major metabolites of P006 by mass spectrometry. This paradigm may be widely adopted as a robust early-stage platform for screening peptide stability to rule out candidates with low in vitro stability, which would likely translate into poor in vivo pharmacokinetics.","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/psc.3539","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10096841","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}

引用次数: 0

Proximity labeling and identification of endogenous client proteins recruited to Y15-based artificial granules tethering a bait protein 内源客户蛋白与 Y15 人工颗粒（系留诱饵蛋白）的接近标记和鉴定。

IF 2.1 4区生物学

Journal of Peptide Science Pub Date : 2023-08-14 DOI: 10.1002/psc.3536

Masahiro Hashimoto, Takayuki Miki, Tatsuya Niwa, Hisakazu Mihara

引用次数: 0

Designed novel nuclear localizing anticancer peptide targets p53 negative regulator MDM2 protein 设计新型核定位抗癌肽靶向p53负调节因子MDM2蛋白。

IF 2.1 4区生物学

Journal of Peptide Science Pub Date : 2023-08-14 DOI: 10.1002/psc.3535

Nabanita Mukherjee, Debmalya Bhunia, Prabir Kumar Garai, Prasenjit Mondal, Surajit Barman, Surajit Ghosh

{"title":"Designed novel nuclear localizing anticancer peptide targets p53 negative regulator MDM2 protein","authors":"Nabanita Mukherjee, Debmalya Bhunia, Prabir Kumar Garai, Prasenjit Mondal, Surajit Barman, Surajit Ghosh","doi":"10.1002/psc.3535","DOIUrl":"10.1002/psc.3535","url":null,"abstract":"Intracellular protein–protein interactions provide a major therapeutic target for the development of peptide-based anticancer therapeutic agents. MDM2 is the 491-residue protein encoded by the MDM2 oncogene. Being a ubiquitin-protein ligase, MDM2 represses the transcription ability of the tumor suppressor p53 by proteasome-mediated degradation. Under typical cellular circumstances, a sustained p53 expression level is maintained by negative regulation of MDM2, whereas under stress conditions, this is alleviated to increase the p53 level. Modulation of MDM2-p53 interaction via fabrication of an MDM2-interacting peptide could be a useful strategy to inhibit subsequent proteasomal degradation of p53 and initiation of p53 signaling leading to the initiation of p53-mediated apoptosis of tumor cells. Here, in this research work, a novel anticancer peptide mPNC-NLS targeting the nucleus and the MDM2 protein (p53 negative regulator) was designed to promote the p53 protein activity for the prevention of cancer. It induces effective apoptosis in both A549 and U87 cells and remains non-cytotoxic to normal lung fibroblast cells (WI38). Further, immunocytochemistry and Western blot results confirm that the designed mPNC-NLS peptide induces the apoptotic death of lung cancer cells via activation of p53 and p21 proteins and remarkably stifled the in vitro growth of 3D multicellular spheroids composed of A549 cells.","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2023-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10001073","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}

引用次数: 0