Peptide Science最新文献

Incorporation of N ‐Glycine Residues Into Collagen to Form Salt Bridges N -甘氨酸残基掺入胶原蛋白形成盐桥

4区生物学

Peptide Science Pub Date : 2026-01-17 DOI: 10.1002/pep2.70024

Rongmao Qiu, Shuting Huang, Jinfeng Su, Xuanxuan Cao, Dechan Lu

{"title":"Incorporation of <i>N</i> ‐Glycine Residues Into Collagen to Form Salt Bridges","authors":"Rongmao Qiu, Shuting Huang, Jinfeng Su, Xuanxuan Cao, Dechan Lu","doi":"10.1002/pep2.70024","DOIUrl":"https://doi.org/10.1002/pep2.70024","url":null,"abstract":"ABSTRACT Collagen, the principal structural protein in mammals, adopts a right‐handed triple helix composed of three left‐handed polyproline‐II helical polypeptide chains featuring repeating Gly‐Xaa‐Yaa tripeptide motifs. Positions Xaa and Yaa frequently contain charged amino acids, which can form salt bridges to stabilize the collagen triple‐helical conformation and fibril formation. Over the past decades, researchers have exploited the charged amino acids to engineer salt bridges for constructing stable collagen‐based biomaterials. However, the use of amino acid analogues to form salt bridges remains largely unexplored. Herein, we report for the first time the incorporation of charged N ‐gly residues into host‐guest collagen mimetic peptides (CMPs) to establish salt bridges. Among these, the EGNap CMP exhibited the highest T m value of 48.2°C, marginally lower than that of the OGP sequence. Molecular modeling indicates that the N ‐gly can form salt bridges with the amino acid, but the distance of these salt bridges is greater than that of KGD. These findings establish a foundational strategy for leveraging N ‐gly‐mediated electrostatic interactions in collagen engineering.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"118 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147920551","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

Pituitary Adenylate Cyclase‐Activating Polypeptide (PACAP) Pretreatment Improves Blood–Brain Barrier (BBB) Integrity in Sepsis by Activating the Wnt3a/β‐Catenin/Claudin‐1 Signaling Pathway 垂体腺苷酸环化酶激活多肽（PACAP）预处理通过激活Wnt3a/β‐Catenin/Claudin‐1信号通路改善脓毒症血脑屏障（BBB）完整性

4区生物学

Peptide Science Pub Date : 2025-04-29 DOI: 10.1002/pep2.70003

Hong-Li Han, Guotao Wang

{"title":"Pituitary Adenylate Cyclase‐Activating Polypeptide (PACAP) Pretreatment Improves Blood–Brain Barrier (BBB) Integrity in Sepsis by Activating the Wnt3a/β‐Catenin/Claudin‐1 Signaling Pathway","authors":"Hong-Li Han, Guotao Wang","doi":"10.1002/pep2.70003","DOIUrl":"https://doi.org/10.1002/pep2.70003","url":null,"abstract":"ABSTRACT The augmentation of blood–brain barrier (BBB) permeability is a key pathological characteristic of sepsis‐associated encephalopathy (SAE). Pituitary adenylate cyclase‐activating polypeptide (PACAP), a well‐known neuropeptide with potent anti‐inflammatory properties, has not yet been investigated for its potential beneficial effects in SAE. In this study, we aimed to explore this aspect. First, the administration of PACAP inhibited the expression of the pro‐inflammatory cytokines interleukin‐1β (IL‐1β) and interleukin‐8 (IL‐8) and mitigated brain vascular injury by reducing the levels of intercellular adhesion molecule‐1 (ICAM‐1) and vascular cell adhesion molecule‐1 (VCAM‐1) in the brains of septic mice. Importantly, PACAP preserved BBB integrity against lipopolysaccharide (LPS)‐induced disruption in septic mice by increasing both the mRNA and protein levels of Claudin‐1. In an in vitro cell culture study, we found that PACAP alleviated the exacerbation of endothelial permeability and increased transendothelial electrical resistance (TEER) against LPS‐induced disruption in bEnd.3 brain endothelial cells, accompanied by an upregulation of Claudin‐1. Consistently, PACAP protected against the reduction of Wnt3a and β‐catenin in response to LPS treatment in bEnd.3 brain endothelial cells. Notably, the knockdown of Wnt3a abolished the beneficial effects of PACAP in reducing endothelial permeability and restoring TEER levels, suggesting that the protective actions of PACAP are mediated through the Wnt3a/β‐catenin signaling pathway. Collectively, these findings demonstrate that PACAP exerts protective effects on BBB integrity in SAE by modulating the Wnt3a/β‐catenin/Claudin‐1 signaling pathway.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"117 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/pep2.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147882394","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

Efficient Screening of Synergistic Antioxidant and AChE Inhibitory Peptides From Sea Cucumber (Stichopus japonicus) Using a Novel Approach Combining De Novo Sequencing and Parallel Peptide Synthesis 利用从头测序和平行肽合成相结合的新方法高效筛选海参（Stichopus japonicus）中协同抗氧化和AChE抑制肽

4区生物学

Peptide Science Pub Date : 2025-04-23 DOI: 10.1002/pep2.70002

Yimeng Li, Gao S, Xiaohui Zhang, Zhuo Cao, Youyou Guo, R. Zhao, Lifan Li, Yonggang Liu, Qi Qin, Bingqing Yi, Guodong Zhao

{"title":"Efficient Screening of Synergistic Antioxidant and <scp>AChE</scp> Inhibitory Peptides From Sea Cucumber (<i>Stichopus japonicus</i>) Using a Novel Approach Combining De Novo Sequencing and Parallel Peptide Synthesis","authors":"Yimeng Li, Gao S, Xiaohui Zhang, Zhuo Cao, Youyou Guo, R. Zhao, Lifan Li, Yonggang Liu, Qi Qin, Bingqing Yi, Guodong Zhao","doi":"10.1002/pep2.70002","DOIUrl":"https://doi.org/10.1002/pep2.70002","url":null,"abstract":"ABSTRACT In this study, we report for the first time that de novo sequencing can be combined with parallel peptide synthesis to facilitate high‐throughput activity screening of biological peptides from natural food. Sea cucumber ( Stichopus japonicus ) intestine was utilized as an example, undergoing gastrointestinal digestion followed by de novo sequencing to predict potential peptide sequences. These peptides were efficiently synthesized for the first time using a readily accessible filter pipette tip as parallel reaction vessels, eliminating the use of any expensive equipment. This method enabled the synthesis of numerous peptides at a milligram scale with microfluidic amino acid flowing through the solid resin. After high‐throughput activity screening, peptide LSPGV was shown to exhibit the most potent antioxidant activity (DPPH radical scavenging activity [DRSA]: 88.96%) and strongest acetylcholinesterase (AChE) inhibition (IC 50 of 7.32 μM) simultaneously. The reduction in paralysis, amyloid‐β (Aβ) aggregation, and AChE activity in vivo was further confirmed in an animal model, Caenorhabditis elegans . 3D structure simulation and molecular docking study were also conducted for LSPGV to illustrate its potential conformation and favorable binding interactions with AChE. As a candidate for Alzheimer's disease (AD) treatment, LSPGV significantly enhances the value of sea cucumber intestine by‐products.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"117 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147331619","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: 1

Salusin‐α Prevents the Development of Abdominal Aortic Aneurysm by Inhibiting the VEGF‐A/VEGF‐R2 Pathway Salusin‐α通过抑制VEGF‐A/VEGF‐R2途径阻止腹主动脉瘤的发展

4区生物学

Peptide Science Pub Date : 2025-02-25 DOI: 10.1002/pep2.70001

Tao Wang, Xijin Zhang, Jianxin Dong

{"title":"Salusin‐α Prevents the Development of Abdominal Aortic Aneurysm by Inhibiting the <scp>VEGF</scp>‐A/<scp>VEGF</scp>‐<scp>R2</scp> Pathway","authors":"Tao Wang, Xijin Zhang, Jianxin Dong","doi":"10.1002/pep2.70001","DOIUrl":"https://doi.org/10.1002/pep2.70001","url":null,"abstract":"ABSTRACT Abdominal aortic aneurysm (AAA) is a vascular disease with a high mortality rate. Currently, the physiological mechanisms of AAA remain poorly understood, and effective treatment options are lacking. Salusin‐α is a vasoactive peptide with various biological functions; however, its effects on AAA development are unknown. In this study, we investigated the potential therapeutic effects of Salusin‐α in AAA using a rodent model. ApoE−/− mice were subcutaneously infused with 1 μg/kg/min of angiotensin II (AngII) (MedChemExpress, USA) using mini‐osmotic pumps to establish an AAA model. First, we observed decreased Salusin‐α levels in the AngII‐induced AAA model. Further investigation demonstrated that Salusin‐α significantly mitigated aneurysm growth in these mice. In addition, we found that Salusin‐α reduced the expression of vascular endothelial growth factor A (VEGF‐A) and VEGF receptor 2, as well as alleviated the inflammatory response by reducing the levels of CC motif ligand 2, CC chemokine receptor type 5, and CXC motif ligand 1. In vitro experiments showed that exposure to AngII down‐regulated Salusin‐α expression in Human umbilical vein endothelial cells (HUVECs). In contrast, Salusin‐α treatment attenuated AngII‐induced cell proliferation and prevented tube formation in HUVECs. Mechanistically, we found that Salusin‐α inhibited the phosphorylation of p38 mitogen‐activated protein kinase, subsequently reducing the levels of nuclear factor‐kappa B (NF‐κB) p65 and luciferase activity of NF‐κB, suggesting that Salusin‐α interferes with the transcriptional activity of NF‐κB. Our findings suggest that targeting Salusin‐α could offer a promising therapeutic strategy to prevent AAA progression.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"117 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/pep2.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147908589","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: 1

An improved synthesis of Compound 11, a unique bicyclic melanocortin-3 antagonist. 独特的双环黑素皮质素-3拮抗剂化合物11的改进合成。

IF 1.7 4区生物学

Peptide Science Pub Date : 2025-01-01 Epub Date: 2024-11-22 DOI: 10.1002/pep2.24385

Stephen T Joy, Naima S Dahir, Roger D Cone, Anna K Mapp

引用次数: 0

Unveiling the Potential Bioactive Peptides Derived From Goat Casein Hydrolysates Based on In Silico Analyses 基于硅分析揭示山羊酪蛋白水解产物的潜在生物活性肽

4区生物学

Peptide Science Pub Date : 2024-10-15 DOI: 10.1002/pep2.24383

Xupeng Bi, Yu Gao, Shiyu Wen, Ziyi Chen, Tong Wu, Jiaqi Wang, Yanmei Hou, Xiaoyu Peng, Wei Li, Lina Pan, Wen Li

{"title":"Unveiling the Potential Bioactive Peptides Derived From Goat Casein Hydrolysates Based on In Silico Analyses","authors":"Xupeng Bi, Yu Gao, Shiyu Wen, Ziyi Chen, Tong Wu, Jiaqi Wang, Yanmei Hou, Xiaoyu Peng, Wei Li, Lina Pan, Wen Li","doi":"10.1002/pep2.24383","DOIUrl":"https://doi.org/10.1002/pep2.24383","url":null,"abstract":"ABSTRACT Bioactive peptides (BAPs) have attracted considerable interest in scientific research due to their heterogeneity in sequence and structure, which underpins various biological functionalities. In this context, goat casein, an abundant by‐product of the dairy industry, emerges as a valuable source of BAPs. The present study undertook a meticulous evaluation of the bioactive potentials of goat casein‐derived peptides through an integrated approach combining computational simulations, high‐throughput screening, and molecular docking techniques. The initial phase involved the enzymatic digestion of goat milk casein using trypsin, followed by the identification of peptides via liquid chromatography–tandem mass spectrometry (LC–MS/MS), uncovering a total of 597 peptides. Subsequent prioritization using the PeptideRanker algorithm identified 70 peptides exhibiting potential bioactivity, as denoted by scores above 0.8. Advanced screening employing the BIOPEP database and the AutoDock and CAMPR4 tools facilitated the elucidation of 16 antioxidant, 59 hypotensive, 63 hypoglycemic, 70 hypolipidemic, and 25 antimicrobial peptides. Molecular docking studies further elucidated the spontaneous nature of the interactions between the peptides and their respective receptors, predominantly mediated by hydrogen bonding and hydrophobic interactions. Four peptides specifying all activities simultaneously were synthesized, and their activities were verified by in vitro experiments. These results not only highlight an effective strategy for the high‐throughput screening of goat casein‐derived peptides but also underscore the potential of utilizing casein as a viable source of functional food ingredients. This study thereby contributes significantly to the expanding field of functional food research, suggesting a sustainable approach to explore the potential of dairy by‐products.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"117 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/pep2.24383","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147330769","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: 1

Insights Into Benzothiazolyl‐Coupled Azetidinone Moieties Toward EGFR Binding and Stability Analysis—Evidence From Molecular Docking and Dynamics Simulation 苯并噻唑基偶氮杂环丁酮分子与表皮生长因子受体的结合及稳定性分析--来自分子对接和动力学模拟的证据

IF 2.4 4区生物学

Peptide Science Pub Date : 2024-08-28 DOI: 10.1002/pep2.24382

Gupta Dheeraj Rajesh, Prarambh S. R. Dwivedi, Abel John Koshy, Anusha S, Ranjitha A, Niyas Rehman, Pankaj Kumar

{"title":"Insights Into Benzothiazolyl‐Coupled Azetidinone Moieties Toward EGFR Binding and Stability Analysis—Evidence From Molecular Docking and Dynamics Simulation","authors":"Gupta Dheeraj Rajesh, Prarambh S. R. Dwivedi, Abel John Koshy, Anusha S, Ranjitha A, Niyas Rehman, Pankaj Kumar","doi":"10.1002/pep2.24382","DOIUrl":"https://doi.org/10.1002/pep2.24382","url":null,"abstract":"Breast cancer, a formidable threat to women's health, mainly manifests in the HER2 subtype, affecting approximately one in five women. Thus, this study endeavors to pioneer novel approaches by exploring the efficacy of benzothiazole‐coupled azetidinone derivatives against EGFR. We aimed to elucidate their potential by employing a comprehensive array of in silico methodologies, including molecular docking, pharmacokinetics profiling, pharmacophore mapping, molecular dynamic simulations, and MMPBSA analysis. Remarkably, our results demonstrate that our designed molecules adhere to Lipinski's rule and comply with essential physiochemical and druggable properties, affirming the promise of these compounds. Ligand MS60 emerges as a lead, showcasing the most substantial interaction with the EGFR receptor, underscored by its impressive docking score of −8.199 kcal/mol. Furthermore, molecular dynamics simulations conducted via GROMACS corroborate the stability of the MS60‐EGFR complex, portraying minimal fluctuations. This assertion is further validated through MMPBSA, PCA analysis, DCCM, and FEL studies, underscoring the robustness of our findings. We have designed the pharmacophore model to unravel critical steric and electronic attributes essential for effective supramolecular interactions with the EGFR receptor. Notably, the presence of the R10, R11, and A4 groups within the ligands underscores their pivotal role in eliciting pharmacological activity, offering valuable insights for further exploration and development.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"32 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142182139","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

Exploring the Therapeutic Potential of Algerian Propolis: GC/MS Profiling, Protective Inclusion Complex, and In Silico Evaluation Against SARS‐CoV‐2 Main Proteases 探索阿尔及利亚蜂胶的治疗潜力：针对 SARS-CoV-2 主要蛋白酶的 GC/MS 分析、保护性包涵复合物和硅学评估

IF 2.4 4区生物学

Peptide Science Pub Date : 2024-08-27 DOI: 10.1002/pep2.24381

Zahra Toutou, Sofiane Fatmi, Nacera Chibani, Katarzyna Pokajewicz, Mohamed Skiba, Piotr P. Wieczorek, Mokrane Iguerouada

{"title":"Exploring the Therapeutic Potential of Algerian Propolis: GC/MS Profiling, Protective Inclusion Complex, and In Silico Evaluation Against SARS‐CoV‐2 Main Proteases","authors":"Zahra Toutou, Sofiane Fatmi, Nacera Chibani, Katarzyna Pokajewicz, Mohamed Skiba, Piotr P. Wieczorek, Mokrane Iguerouada","doi":"10.1002/pep2.24381","DOIUrl":"https://doi.org/10.1002/pep2.24381","url":null,"abstract":"Propolis, a bee product, is renowned globally for its diverse pharmacological activities attributed to its phenolic compounds, flavonoids, and terpenes. This study aims to identify the chemical compounds in Algerian raw propolis and evaluate the protective potential of its inclusion complex. Gas chromatography–mass spectrometry (GC/MS), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA) were used for chemical characterization. Additionally, molecular docking against SARS‐COVID‐2 main proteases and ADMET profiling were conducted. The analysis revealed α‐pinene (25.29%–11.04%) and limonene (22.46%–12.88%) as the major components in raw propolis and its complex. DSC/TGA analysis demonstrated the protective effect of encapsulated molecules, with limonene and α‐pinene showing high activity against SARS‐COVID‐2 main proteases 7N5Z, 6LU7, and 7E6L, with docking scores of −5.71, −5.61, and −5.10 kcal/mol, respectively. This study highlights the potential of propolis constituents as drug candidates against the SARS‐COVID‐2 pandemic.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"23 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142182136","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

Analogs of Cyclic Peptide Mortiamide‐D From Marine Fungi Have Improved Membrane Permeability and Kill Drug‐Resistant Melanoma Cells 海洋真菌中的环肽 Mortiamide-D 类似物具有更好的膜渗透性，能杀死耐药性黑色素瘤细胞

IF 2.4 4区生物学

Peptide Science Pub Date : 2024-08-17 DOI: 10.1002/pep2.24380

Catherine Bergeron, Christopher Bérubé, Henry Lamb, Yasuko Koda, David J. Craik, Sónia Troeira Henriques, Normand Voyer, Nicole Lawrence

{"title":"Analogs of Cyclic Peptide Mortiamide‐D From Marine Fungi Have Improved Membrane Permeability and Kill Drug‐Resistant Melanoma Cells","authors":"Catherine Bergeron, Christopher Bérubé, Henry Lamb, Yasuko Koda, David J. Craik, Sónia Troeira Henriques, Normand Voyer, Nicole Lawrence","doi":"10.1002/pep2.24380","DOIUrl":"https://doi.org/10.1002/pep2.24380","url":null,"abstract":"Targeted melanoma therapies, including treatment with the small molecule drug dabrafenib, can become ineffective due to acquired drug resistance. Dabrafenib targets BRAF‐V600E, a mutation that is present in more than half of melanoma cancers. Therefore, drug discovery efforts need to explore alternative candidate molecules that selectively target and kill melanoma cells via mechanisms different to those of current drugs. Marine fungi are an underexplored resource for bioactive molecules. Mortiamide‐D, a seven amino acid cyclic peptide from Mortierella sp, is an example molecule with desirable features for drug development. We synthesized mortiamide‐D and three rationally designed analogs and observed modest micromolar activity against HT144 melanoma cells that are sensitive or resistant to dabrafenib. By contrast, mortiamide‐D and analogs did not kill noncancer HaCaT cells at these concentrations. Substitution of D‐Ile at position 7 with D‐Arg improved membrane permeability and enhanced potency against HT144 cells via a mode‐of‐action that includes perturbation of mitochondrial membrane potential. These studies suggest the potential of mortiamides as modifiable scaffolds for developing a new class of molecule for targeting melanoma cells.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"50 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142182137","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

In Silico Analysis of Conformational Dynamics and Energetic Landscapes of Putative Insulinase PF11_0189 From the Plasmodium falciparum Genome With Insulin‐Derived Peptides: Approach to Rationale Design of Insulin Peptide‐Based Inhibitors 用胰岛素衍生肽对恶性疟原虫基因组中假定胰岛素酶 PF11_0189 的构象动力学和能谱进行硅学分析：基于胰岛素肽的抑制剂的合理设计方法

IF 2.4 4区生物学

Peptide Science Pub Date : 2024-08-12 DOI: 10.1002/pep2.24377

Prabhash Jyoti Mahanta, Kimjolly Lhouvum

{"title":"In Silico Analysis of Conformational Dynamics and Energetic Landscapes of Putative Insulinase PF11_0189 From the Plasmodium falciparum Genome With Insulin‐Derived Peptides: Approach to Rationale Design of Insulin Peptide‐Based Inhibitors","authors":"Prabhash Jyoti Mahanta, Kimjolly Lhouvum","doi":"10.1002/pep2.24377","DOIUrl":"https://doi.org/10.1002/pep2.24377","url":null,"abstract":"Glucose abnormality is one of the atypical symptoms mostly overlooked during severe malaria. Screening for proteases involved in glucose abnormality suggests a potential new drug target. PF11_0189 is a putative insulin degrading enzyme found in the genome of Plasmodium falciparum. In silico approach revealed that PF11_0189 is similar to the metalloproteases exhibiting a zinc binding motif. The substrate binding region of PF11_0189 catalytic domain is lined by residues of a mixed nature, enabling the accommodation of both hydrophobic and hydrophilic residues from substrates. Analysis of each amino acid position from combinatorial peptide library suggests Thr and Ser to be the most crucial residues as upon its mutation significant improvement is observed in the binding. The peptides P‐21 (VPICSLY), P‐70 (TMICVLY), and P‐121 (AVICSLY) demonstrate significantly better interaction within the active site than a template peptide (TSICSLY). Molecular dynamic simulations confirm the complex's integrity, with all structures within the qualitative limit of compactness and stability during the simulation time. Principal component analysis (PCA) reveals major conformational motions and different energy landscapes, while dynamic cross‐correlation matrix (DCCM) highlights residue interactions of the complexes. The insights obtained through computational methods provide clues about substrate selectivity in PF11_0189, which can be utilized for peptide‐based therapeutics against severe malaria.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"32 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142182138","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