Peptide Science最新文献_第9页

Peptides and peptidomimetics as therapeutic agents for Covid-19. 作为 Covid-19 治疗药物的肽和肽拟物。

IF 1.5 4区生物学

Peptide Science Pub Date : 2022-01-01 Epub Date: 2021-10-11 DOI: 10.1002/pep2.24245

Achyut Dahal, Jafrin Jobayer Sonju, Konstantin G Kousoulas, Seetharama D Jois

引用次数: 0

Issue Information 问题信息

IF 2.4 4区生物学

Peptide Science Pub Date : 2022-01-01 DOI: 10.1002/pep2.24257

引用次数: 0

Computational design of stapled peptide inhibitor against SARS‐CoV‐2 receptor binding domain 抗SARS - CoV - 2受体结合域的钉接肽抑制剂的计算设计

IF 2.4 4区生物学

Peptide Science Pub Date : 2021-12-30 DOI: 10.1002/pep2.24267

A. Choudhury, A. Maity, S. Chakraborty, R. Chakrabarti

{"title":"Computational design of stapled peptide inhibitor against SARS‐CoV‐2 receptor binding domain","authors":"A. Choudhury, A. Maity, S. Chakraborty, R. Chakrabarti","doi":"10.1002/pep2.24267","DOIUrl":"https://doi.org/10.1002/pep2.24267","url":null,"abstract":"Since its first detection in 2019, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) has been the cause of millions of deaths worldwide. Despite the development and administration of different vaccines, the situation is still worrisome as the virus is constantly mutating to produce newer variants some of which are highly infectious. This raises an urgent requirement to understand the infection mechanism and thereby design therapeutic‐based treatment for COVID‐19. The gateway of the virus to the host cell is mediated by the binding of the receptor binding domain (RBD) of the virus spike protein to the angiotensin‐converting enzyme 2 (ACE2) of the human cell. Therefore, the RBD of SARS‐CoV‐2 can be used as a target to design therapeutics. The α1 helix of ACE2, which forms direct contact with the RBD surface, has been used as a template in the current study to design stapled peptide therapeutics. Using computer simulation, the mechanism and thermodynamics of the binding of six stapled peptides with RBD have been estimated. Among these, the one with two lactam stapling agents has shown binding affinity, sufficient to overcome RBD‐ACE2 binding. Analyses of the mechanistic detail reveal that a reorganization of amino acids at the RBD‐ACE2 interface produces favorable enthalpy of binding whereas conformational restriction of the free peptide reduces the loss in entropy to result higher binding affinity. The understanding of the relation of the nature of the stapling agent with their binding affinity opens up the avenue to explore stapled peptides as therapeutic against SARS‐CoV‐2.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"113 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2021-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80623589","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: 4

Generation of inhibitory peptides for IKKε from a kinase‐focused phage library of helix‐loop‐helix peptides 从螺旋-环-螺旋肽的激酶聚焦噬菌体文库中产生IKKε抑制肽

IF 2.4 4区生物学

Peptide Science Pub Date : 2021-12-15 DOI: 10.1002/pep2.24253

Kousuke Mihara, Natsumi Nakajima, I. Fujii, Daisuke Fujiwara

{"title":"Generation of inhibitory peptides for IKKε from a kinase‐focused phage library of helix‐loop‐helix peptides","authors":"Kousuke Mihara, Natsumi Nakajima, I. Fujii, Daisuke Fujiwara","doi":"10.1002/pep2.24253","DOIUrl":"https://doi.org/10.1002/pep2.24253","url":null,"abstract":"Conformationally constrained peptides are attracting attention as peptide‐based molecular tools in chemical biology and drug discovery because of their desirable properties such as high selectivity for target binding and stability toward proteolytic enzymes. We previously reported a protein kinase–focused helix‐loop‐helix (HLH) peptide library. The library was constructed by phage display and subsequent chemical modification with adenosine that was employed as an anchor molecule binding to the ATP‐binding pocket of kinase. Here, we discovered and characterized HLH peptides that bind to and inhibit the serine/threonine protein kinase IKKε, a member of the IκB kinase (IKK) family. Screening the library against IKKε identified de novo HLH peptides binding to the kinase. One of the peptides, IKK‐05, showed a high α‐helical content and inhibited IKKε with a mixed‐inhibition mechanism with respect to ATP. The adenosine‐tethering peptide Adc‐IKK‐05 demonstrated significantly enhanced enzyme inhibition activity, indicating a bivalency effect in binding to IKKε. In addition, Adc‐IKK‐05 showed the highest inhibitory activity against IKKε of the IKK family members and other families tested. The peptides obtained in this research can be developed as molecular tools to study the biological functions of IKKε and to obtain structural insights for the design of selective IKKε inhibitors.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2021-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46074409","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

Unambiguous characterization of PEGylation site on human amylin by two‐dimensional nuclear magnetic resonance spectroscopy 二维核磁共振波谱对人胰淀素聚乙二醇化位点的模糊表征

IF 2.4 4区生物学

Peptide Science Pub Date : 2021-12-11 DOI: 10.1002/pep2.24252

L. M. T. Lima, T. S. Araújo, M. Almeida

{"title":"Unambiguous characterization of PEGylation site on human amylin by two‐dimensional nuclear magnetic resonance spectroscopy","authors":"L. M. T. Lima, T. S. Araújo, M. Almeida","doi":"10.1002/pep2.24252","DOIUrl":"https://doi.org/10.1002/pep2.24252","url":null,"abstract":"Amylin is a 37‐residue peptide hormone, which is co‐secreted with insulin and prevents postprandial spikes in blood glycemia by slowing gastric emptying and promoting satiety. Amylin is prone to aggregate into oligomers and amyloid fibrils, which is related to the onset of type 2 diabetes, and hampers its use as a biopharmaceutical. To overcome the instability and extend its in vivo half‐life it has been proposed the conjugation of amylin with polyethylene glycol (PEG) at the HNζ or the HNα amines of Lys1. Here we used two‐dimensional nuclear magnetic resonance spectra aiming the unambiguous identification of the site of covalent modification on amylin. The coupling of PEG causes both a substantial decrease in the chemical exchange of their HN and alterations in the chemical shifts at both the HN and the neighborhood hydrocarbon groups including CHα, CHδ and CHε of Lys1. Additional analysis of chemical shifts indicates alteration in the HNα solvent accessibility of residues Cys2, Asn3, Ala5, Cys7, and Gln10, and confirmed the presence of oxidized Cys2 and Cys7. We believe that the methodology described here is a reference for the characterization of chemical coupling of a number of biopharmaceuticals.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2021-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48293618","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

Leucine rich repeat kinase 2 (LRRK2) peptide modulators: Recent advances and future directions 富含亮氨酸重复激酶2（LRRK2）肽调节剂：最新进展和未来方向

IF 2.4 4区生物学

Peptide Science Pub Date : 2021-12-11 DOI: 10.1002/pep2.24251

Leah G. Helton, H. Rideout, F. Herberg, E. Kennedy

{"title":"Leucine rich repeat kinase 2 (LRRK2) peptide modulators: Recent advances and future directions","authors":"Leah G. Helton, H. Rideout, F. Herberg, E. Kennedy","doi":"10.1002/pep2.24251","DOIUrl":"https://doi.org/10.1002/pep2.24251","url":null,"abstract":"Leucine rich repeat kinase 2 (LRRK2) is the most common genetic contributor to Parkinson's disease (PD), a complex neurodegenerative disorder affecting nearly 10 million people worldwide. Pathogenic mutations within LRRK2 often induce increased kinase activity, an effect that can be abolished with many small molecule inhibitors; however, these small molecule inhibitors are currently limited by their toxicities. Given the large and complex nature of LRRK2, more recent efforts have focused on protein–protein interactions (PPIs) involving LRRK2 and how they can contribute to PD. Here, we review recently resolved structures of LRRK2 and highlight unique interfaces driving both catalytic and non‐catalytic activities. Combining new structural information with established in vitro and in vivo data clarifies the role of PPIs in driving LRRK2‐mediated disease pathogenesis. Since constrained peptides and peptidomimetics have the potential to engage with elongated, hydrophobic interfaces that were previously considered “undruggable,” they may provide a unique handle for LRRK2 targeting. Here, we discuss the use of constrained peptides and peptidomimetics to target LRRK2 as a strategy to downregulate its pathological activity.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2021-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44970207","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

A conserved β‐bulge glycine residue facilitates folding and increases stability of the mouse α‐defensin cryptdin‐4 保守的β凸起甘氨酸残基促进小鼠α防御素密码子蛋白-4的折叠并增加其稳定性

IF 2.4 4区生物学

Peptide Science Pub Date : 2021-11-26 DOI: 10.1002/pep2.24250

R. Clark, Thanh Huyen Phan, A. Song, A. Ouellette, A. C. Conibear, K. Rosengren

{"title":"A conserved β‐bulge glycine residue facilitates folding and increases stability of the mouse α‐defensin cryptdin‐4","authors":"R. Clark, Thanh Huyen Phan, A. Song, A. Ouellette, A. C. Conibear, K. Rosengren","doi":"10.1002/pep2.24250","DOIUrl":"https://doi.org/10.1002/pep2.24250","url":null,"abstract":"Defensins are key components of both innate and adaptive immune responses to pathogens. Cryptdins are mouse alpha‐defensins that are secreted from Paneth cells in the small intestine and have disulfide‐stabilised structures and antibacterial activities against both Gram‐positive and Gram‐negative bacteria. The folding and three‐dimensional structures of alpha‐defensins are thought to depend on a conserved glycine residue that forms a β‐bulge. Here we investigated the role of this conserved glycine at position 19 of cryptdin‐4 (Crp4) in terms of the folding, structure and stability. A Crp4 variant with D‐Ala at position 19 folded efficiently, was stabilised by a large number of hydrogen bonds, and resisted proteolysis in simulated intestinal fluid. Although a variant with L‐Ala at position 19 was able to adopt the correct fold, it showed less efficient folding and was degraded more rapidly than the D‐Ala variant. These results demonstrate the key role that glycine residues can have in folding of bioactive peptides and can provide insights to guide design of stable antimicrobial peptides that fold efficiently.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2021-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44169021","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

Issue Information 问题信息

IF 2.4 4区生物学

Peptide Science Pub Date : 2021-11-01 DOI: 10.1002/pep2.24249

引用次数: 0

Identifying blood‐brain barrier peptides by using amino acids physicochemical properties and features fusion method 利用氨基酸理化性质和特征融合方法鉴定血脑屏障肽

IF 2.4 4区生物学

Peptide Science Pub Date : 2021-10-28 DOI: 10.1002/pep2.24247

Hongliang Zou

{"title":"Identifying blood‐brain barrier peptides by using amino acids physicochemical properties and features fusion method","authors":"Hongliang Zou","doi":"10.1002/pep2.24247","DOIUrl":"https://doi.org/10.1002/pep2.24247","url":null,"abstract":"Blood‐brain barrier peptides (BBPs) play a promising role in current drug study of central nervous system diseases. Hence, it is an urgent need to rapidly and accurately discriminating BBPs from non‐BBPs. Experimental approaches are the first choice, however, these methods are expensive and take a lot of time. Thus, more and more researchers focused their attention on computational models. In current work, we developed a support vector machine (SVM) based model to identify BBPs. First, amino acids physicochemical properties were employed to represent peptide sequences, and Pearson's correlation coefficient (PCC) and maximal information coefficient (MIC) were applied to extract useful information. Then, similarity network fusion algorithm was utilized to integrate these two different kinds of features. Next, Fisher algorithm was used to pick out the discriminative features. Finally, these selected features were input into SVM for distinguishing BBPs from non‐BBPs. The proposed model achieved 100.00% and 89.47% classification accuracies on training and independent datasets, respectively. Additionally, we found that pK2 (NH3) property of amino acid plays a key role in discriminating BBPs from non‐BBPs. The results showed that our proposed method is effective, and achieved a significantly improvement in identifying BBPs, as compared with the state‐of‐the‐art approach. The Matlab codes and datasets are freely available at https://figshare.com/articles/online_resource/iBBPs_zip/14723766.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2021-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43903161","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: 3

Antimicrobial peptides provide wider coverage for targeting drug‐resistant bacterial pathogens 抗菌肽为靶向耐药细菌病原体提供了更广泛的覆盖范围

IF 2.4 4区生物学

Peptide Science Pub Date : 2021-10-01 DOI: 10.1002/pep2.24246

Anna S. Amiss, S. Henriques, N. Lawrence

引用次数: 1