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.
{"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}
Pub Date : 2025-01-01Epub Date: 2024-11-22DOI: 10.1002/pep2.24385
Stephen T Joy, Naima S Dahir, Roger D Cone, Anna K Mapp
The melanocortin-3 receptor (MC3R) is a G-protein coupled receptor that regulates appetite and is a potential therapeutic target for anorexia and weight loss treatments. The report of a highly selective synthetic antagonist of MC3R, Cpd11, represents a major advance towards therapeutic targeting of MC3R. However, Cpd11 is challenging to access synthetically, severely limiting its use and additional structural optimization. Here, we outline an improved synthesis of Cpd11 that addresses three major synthetic challenges, including the formation of Cpd11's structurally unique bicyclic core. With these changes, Cpd11 was readily produced (2.3 mg from a .05 mmol scale versus << 0.1 mg using the original synthetic methodology) and utilized in MC3R studies in C57BL/6J male mice. Thus, this new approach will increase the accessibility of Cpd11 and is translatable to related bicyclic agonists and antagonists for other melanocortin receptors and may have general applicability toward the synthesis of other multicyclic poly-cysteine peptides.
{"title":"An improved synthesis of Compound 11, a unique bicyclic melanocortin-3 antagonist.","authors":"Stephen T Joy, Naima S Dahir, Roger D Cone, Anna K Mapp","doi":"10.1002/pep2.24385","DOIUrl":"10.1002/pep2.24385","url":null,"abstract":"<p><p>The melanocortin-3 receptor (MC3R) is a G-protein coupled receptor that regulates appetite and is a potential therapeutic target for anorexia and weight loss treatments. The report of a highly selective synthetic antagonist of MC3R, Cpd11, represents a major advance towards therapeutic targeting of MC3R. However, Cpd11 is challenging to access synthetically, severely limiting its use and additional structural optimization. Here, we outline an improved synthesis of Cpd11 that addresses three major synthetic challenges, including the formation of Cpd11's structurally unique bicyclic core. With these changes, Cpd11 was readily produced (2.3 mg from a .05 mmol scale versus << 0.1 mg using the original synthetic methodology) and utilized in MC3R studies in C57BL/6J male mice. Thus, this new approach will increase the accessibility of Cpd11 and is translatable to related bicyclic agonists and antagonists for other melanocortin receptors and may have general applicability toward the synthesis of other multicyclic poly-cysteine peptides.</p>","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"117 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12124840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199838","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}
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.
{"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}
Gupta Dheeraj Rajesh, Prarambh S. R. Dwivedi, Abel John Koshy, Anusha S, Ranjitha A, Niyas Rehman, Pankaj Kumar
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.
{"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}
Zahra Toutou, Sofiane Fatmi, Nacera Chibani, Katarzyna Pokajewicz, Mohamed Skiba, Piotr P. Wieczorek, Mokrane Iguerouada
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.
{"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}
Catherine Bergeron, Christopher Bérubé, Henry Lamb, Yasuko Koda, David J. Craik, Sónia Troeira Henriques, Normand Voyer, Nicole Lawrence
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.
{"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 <jats:italic>Mortierella</jats:italic> 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}
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.
{"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 <jats:italic>Plasmodium falciparum.</jats:italic> 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}
Antimicrobial peptides (AMPs) are being studied for their potential in addressing microbial resistance, a significant issue in treating infections. More than 22,500 AMPs are listed in the database, but their clinical use faces challenges like instability and selectivity. Nanodrug delivery systems are now seen as a beneficial method to improve the effectiveness of AMPs. These systems can shield AMPs from degradation, enhance their availability, and deliver them to specific infection sites, enhancing their ability to combat resistance. One example is liposomal nanoparticles loaded with a mix of AMPs, targeting drug‐resistant bacteria directly. Strategies to develop novel AMPs through engineering methods, including design approaches, computational techniques, and modifications for stability, are discussed in this review. Combinatorial approaches with antibiotics, patents, and clinical trials involving AMPs against infections are also considered, highlighting the potential of AMPs in battling microbial resistance.
{"title":"Empowering Antimicrobial Peptides: Harnessing Nanotechnology and Engineering Strategies to Combat Microbial Resistance","authors":"Dubey Avinash, Anjali Bisht, Manish Kumar, Shubham Thakur, Preeti Patel, Balak Das Kurmi","doi":"10.1002/pep2.24376","DOIUrl":"https://doi.org/10.1002/pep2.24376","url":null,"abstract":"Antimicrobial peptides (AMPs) are being studied for their potential in addressing microbial resistance, a significant issue in treating infections. More than 22,500 AMPs are listed in the database, but their clinical use faces challenges like instability and selectivity. Nanodrug delivery systems are now seen as a beneficial method to improve the effectiveness of AMPs. These systems can shield AMPs from degradation, enhance their availability, and deliver them to specific infection sites, enhancing their ability to combat resistance. One example is liposomal nanoparticles loaded with a mix of AMPs, targeting drug‐resistant bacteria directly. Strategies to develop novel AMPs through engineering methods, including design approaches, computational techniques, and modifications for stability, are discussed in this review. Combinatorial approaches with antibiotics, patents, and clinical trials involving AMPs against infections are also considered, highlighting the potential of AMPs in battling microbial resistance.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"15 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141885875","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}
Nurkhodja Mukhamedov, Akmal M. Asrorov, Muzaffar Kayumov, Ahmidin Wali, Haji Akber Aisa, Sharafitdin Mirzaakhmedov, Abulimiti Yili
Zinc is the second most valuable microelement after iron, according to its abundance in the human body. Supplementation of this metal is not straightforward because of several factors like phytates and interference of other minerals during gastrointestinal digestion. For the last several years, intensive research has been developing new forms of zinc supplements based on zinc‐binding peptides from food products. Except for the advantages of supplementation, zinc‐peptide complexes are expected to be drug candidates against various diseases. Zinc supplementation can be improved by protein hydrolysates and peptides due to their zinc‐binding ability. They enhance zinc supplementation and contribute to preventing conditions leading to zinc deficiency that cause various diseases. Research on food‐derived zinc‐binding peptides is progressing in two directions: the isolation and identification of individual peptides (1) and the preparation of zinc complexes of protein hydrolysates (2). Both approaches are primarily aimed at developing effective mineral supplements, although some work on the second approach is also related to nutrition and therapy. Because zinc–protein hydrolysate complexes are nonstandardized mixtures of peptides, their biological activity mechanisms can be difficult to study. Therefore, it is important to focus more research on the biological activity of individual zinc‐binding complexes and their zinc complexes. This work reviewed recent advances in isolating and identifying zinc‐binding peptides from food sources, preparing protein hydrolysate–zinc complexes, and their biological activities. The established sequences of zinc‐binding peptides have been compiled into a table to review their amino‐acid composition and sequence. We also highlighted approaches for isolating and determining the zinc‐binding capacity of peptides in this class. The structural features of peptides affecting their zinc‐binding property were discussed in one section.
{"title":"Food Protein‐Derived Zinc‐Binding Peptides: Isolation, Purification, and Biological Aspects","authors":"Nurkhodja Mukhamedov, Akmal M. Asrorov, Muzaffar Kayumov, Ahmidin Wali, Haji Akber Aisa, Sharafitdin Mirzaakhmedov, Abulimiti Yili","doi":"10.1002/pep2.24369","DOIUrl":"https://doi.org/10.1002/pep2.24369","url":null,"abstract":"Zinc is the second most valuable microelement after iron, according to its abundance in the human body. Supplementation of this metal is not straightforward because of several factors like phytates and interference of other minerals during gastrointestinal digestion. For the last several years, intensive research has been developing new forms of zinc supplements based on zinc‐binding peptides from food products. Except for the advantages of supplementation, zinc‐peptide complexes are expected to be drug candidates against various diseases. Zinc supplementation can be improved by protein hydrolysates and peptides due to their zinc‐binding ability. They enhance zinc supplementation and contribute to preventing conditions leading to zinc deficiency that cause various diseases. Research on food‐derived zinc‐binding peptides is progressing in two directions: the isolation and identification of individual peptides (1) and the preparation of zinc complexes of protein hydrolysates (2). Both approaches are primarily aimed at developing effective mineral supplements, although some work on the second approach is also related to nutrition and therapy. Because zinc–protein hydrolysate complexes are nonstandardized mixtures of peptides, their biological activity mechanisms can be difficult to study. Therefore, it is important to focus more research on the biological activity of individual zinc‐binding complexes and their zinc complexes. This work reviewed recent advances in isolating and identifying zinc‐binding peptides from food sources, preparing protein hydrolysate–zinc complexes, and their biological activities. The established sequences of zinc‐binding peptides have been compiled into a table to review their amino‐acid composition and sequence. We also highlighted approaches for isolating and determining the zinc‐binding capacity of peptides in this class. The structural features of peptides affecting their zinc‐binding property were discussed in one section.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"67 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141777242","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}
Krista K. Alexander, Michalis Kentros, Leah G. Helton, Dimitris Tantis‐Tapeinos, Timothy J. LeClair, Fredejah T. Royer, Neil J. Grimsey, Alexia V. Polissidis, Eileen J. Kennedy, Hardy J. Rideout
Mutations in the gene encoding leucine‐rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson's disease (PD). The reduced penetrance of mutations in the LRRK2 gene has also led to variants appearing in seemingly sporadic forms of the disease. Kinase inhibition effectively blocks neuronal death and small‐molecule Class I inhibitors are proceeding through clinical trials in multiple PD cohorts. The toxic interaction between mutant LRRK2 and FADD lies downstream of its kinase activity and is required to induce neuronal death. The present study aimed to determine whether the FADD‐LRRK2 interface could be disrupted and what effects this may have on neuroprotection. A series of constrained peptides were designed to mimic the alpha‐helical protein interaction interface between the LRRK2 armadillo region and the death domain of FADD. These peptide‐based protein–protein interaction inhibitors significantly reduced this interaction and blocked apoptotic death of primary neurons expressing G2019S‐LRRK2. This work has identified novel constrained peptides that disrupt the LRRK2‐FADD interface and downregulate mutant LRRK2‐induced neuronal death in an allosteric manner, thereby providing a potential alternative therapeutic approach for PD.
{"title":"Disruption of the LRRK2‐FADD Interface Using Constrained Peptides","authors":"Krista K. Alexander, Michalis Kentros, Leah G. Helton, Dimitris Tantis‐Tapeinos, Timothy J. LeClair, Fredejah T. Royer, Neil J. Grimsey, Alexia V. Polissidis, Eileen J. Kennedy, Hardy J. Rideout","doi":"10.1002/pep2.24374","DOIUrl":"https://doi.org/10.1002/pep2.24374","url":null,"abstract":"Mutations in the gene encoding leucine‐rich repeat kinase 2 (<jats:italic>LRRK2</jats:italic>) are the most common cause of familial Parkinson's disease (PD). The reduced penetrance of mutations in the LRRK2 gene has also led to variants appearing in seemingly sporadic forms of the disease. Kinase inhibition effectively blocks neuronal death and small‐molecule Class I inhibitors are proceeding through clinical trials in multiple PD cohorts. The toxic interaction between mutant LRRK2 and FADD lies downstream of its kinase activity and is required to induce neuronal death. The present study aimed to determine whether the FADD‐LRRK2 interface could be disrupted and what effects this may have on neuroprotection. A series of constrained peptides were designed to mimic the alpha‐helical protein interaction interface between the LRRK2 armadillo region and the death domain of FADD. These peptide‐based protein–protein interaction inhibitors significantly reduced this interaction and blocked apoptotic death of primary neurons expressing G2019S‐LRRK2. This work has identified novel constrained peptides that disrupt the LRRK2‐FADD interface and downregulate mutant LRRK2‐induced neuronal death in an allosteric manner, thereby providing a potential alternative therapeutic approach for PD.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"24 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141777243","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}
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