Peptide Science最新文献

英文中文

Promotion of 11/9‐helical folding in α/β‐peptides containing β2‐homoalanine residue 促进含有β2-高丙氨酸残基的α/β肽的11/9螺旋折叠

IF 2.4 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptide Science

Pub Date : 2021-09-23 DOI: 10.1002/pep2.24244

Hyerim Yoon, Jaeyeon Lee, Philjae Kang, Soo Hyuk Choi

The 11/9‐helix is one of nontraditional helices available to α/β‐peptides with alternating residue types. Several β‐amino acid residues are known to promote 11/9‐helical folding with two types of intramolecular hydrogen bonds. Both β2‐amino acids and β3‐amino acids are common acyclic β‐amino acids that can be regarded as homologs of α‐amino acids with the same side chain group. However, β2‐amimo acids have not been widely used as much as β3‐amino acids partly because β2‐residue is believed to be not as strong as β3‐residue in promoting a distinct conformation. Here we report 11/9‐helical folding of α/β‐peptides that consist of L‐α‐alanine and (S)‐β2‐homoalanine with residue alternation. In addition, circular dichroism study reveals that β2‐homoalanine promotes 11/9‐helical folding more strongly than β3‐homoalanine in polar protic solvent conditions.

11/9螺旋是可用于具有交替残基类型的α/β肽的非传统螺旋之一。已知几个β氨基酸残基通过两种类型的分子内氢键促进11/9螺旋折叠。β2-氨基酸和β3-氨基酸都是常见的无环β-氨基酸，可以视为具有相同侧链基团的α-氨基酸的同源物。然而，β2-氨基酸并没有像β3-氨基酸那样被广泛使用，部分原因是β2-残基被认为在促进不同构象方面不如β3-残基强。在这里，我们报道了由L-α-丙氨酸和（S）-β2-高丙氨酸组成的α/β-肽的11/9螺旋折叠，具有残基交替。此外，圆二色性研究表明，在极性质子溶剂条件下，β2-高丙氨酸比β3-高丙氨酸更能促进11/9螺旋折叠。

引用次数: 0

Effect of C‐terminal and N‐terminal dimerization and alanine scanning on antibacterial activity of the analogs of the peptide p‐BthTX‐I C端和N端二聚化及丙氨酸扫描对肽p - BthTX - I类似物抗菌活性的影响

IF 2.4 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptide Science

Pub Date : 2021-09-16 DOI: 10.1002/pep2.24243

N. Santos-Filho, Gabriela Marinho Righetto, Marina Rodrigues Pereira, Julia P. Piccoli, Larissa Mathias Teizen Almeida, Thainá Cristina Leal, I. L. Camargo, E. Cilli

The peptide (p‐BthTX‐I)2 [(KKYRYHLKPFCKK)2] and its analog des‐Lys12,Lys13‐(p‐BthTX‐I)2 [(KKYRYHLKPFC)2] showed activity against bacteria and potential specificity against prokaryotic cells. In this study, we synthesized the peptide des‐Cys11,Lys12,Lys13‐(p‐BthTX‐I)2K [(KKYRYHLKPF)2K] with a Lys instead of a Cys residue in the dimerization step, beginning the SPPS with Fmoc‐Lys(Fmoc)‐OH. This change avoided Cys oxidation, decreasing one step in the original peptide synthesis and obtaining a smaller and more stable peptide. The antimicrobial activity of the peptide des‐Cys11,Lys12,Lys13‐(p‐BthTX‐I)2K was superior to that of the (p‐BthTX‐I)2 peptide against the bacterial strains tested. Additionally, to evaluate the impact of the linker position on peptide dimerization, we synthesized peptide E(p‐BthTX‐I)2 [E(KKYRYHLKPFCKK)2] using Fmoc‐Glu‐OH at the end of the synthesis. This N‐terminal dimeric peptide did not increase the antibacterial activity, indicating that the free N‐terminal is essential for (p‐BthTX‐I)2 activity. Additionally, we observed lower antimicrobial activity by substituting positive and aromatic residues with Ala in the alanine scanning assay, irrespective of the amino acid change, indicating that each amino acid is essential for the mechanism of action of the peptide. Therefore, we demonstrated that the (p‐BthTX‐I)2 analog, which is shorter and synthesized by an easier process leading to a more stable peptide, is the most antibacterial active peptide against multidrug‐resistant bacteria and does not increase hemolysis activity.

肽(p‐BthTX‐I)2 [(kkyryhlpfckk)2]及其类似物des‐Lys12,Lys13‐(p‐BthTX‐I)2 [(KKYRYHLKPFC)2]显示出对细菌的活性和对原核细胞的潜在特异性。在本研究中，我们在二聚化步骤中用赖氨酸代替赖氨酸残基合成了肽des‐Cys11,Lys12,Lys13‐(p‐BthTX‐I)2K [(KKYRYHLKPF)2K]，以Fmoc‐Lys(Fmoc)‐OH开始SPPS。这种改变避免了Cys氧化，使原肽合成减少了一步，得到了更小更稳定的肽。肽des‐Cys11、Lys12、Lys13‐(p‐BthTX‐I)2K对细菌的抑菌活性优于肽(p‐BthTX‐I)2。此外，为了评估连接体位置对肽二聚化的影响，我们在合成结束时使用Fmoc‐Glu‐OH合成了肽E(p‐BthTX‐I)2 [E(KKYRYHLKPFCKK)2]。该N端二聚体肽没有增加抗菌活性，表明游离N端对(p - BthTX - I)2活性至关重要。此外，我们观察到，在丙氨酸扫描实验中，用Ala取代阳性和芳香残基的抗菌活性较低，而与氨基酸的变化无关，这表明每种氨基酸对肽的作用机制都是必不可少的。因此，我们证明了(p‐BthTX‐I)2类似物，它更短，更容易合成，从而产生更稳定的肽，是对多药耐药细菌最具抗菌活性的肽，并且不会增加溶血活性。

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引用次数: 8

Issue Information 问题信息

IF 2.4 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptide Science

Pub Date : 2021-09-01 DOI: 10.1002/pep2.24242

引用次数: 0

De novo design of metal‐binding cleft in a Trp‐Trp stapled thermostable β‐hairpin peptide Trp-Trp缝合的热稳定β发夹肽中金属结合裂缝的从头设计

IF 2.4 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptide Science

Pub Date : 2021-08-18 DOI: 10.1002/pep2.24240

Muralikrishna Lella, R. Mahalakshmi

Metals are important molecules in protein biochemistry, as they are involved in various essential biochemical processes. Inspired by the coordination chemistry of metal‐binding proteins, and to improvise the stability of recognition motifs, here we present the design of hyperstable stapled β‐hairpin with a defined metal‐binding cleft. We achieved this by establishing Trp‐Trp covalent cross‐linking in a long‐chain 16‐residue β‐hairpin scaffold, and incorporating a stereospecific Cys2‐His2 tetrad as the metal‐binding cleft. This water‐soluble peptide showed broad metal‐binding properties, with Cu2+ specificity. Importance of the Cys‐His tetrad in metal ion selectivity was established with Asp/Glu substitutions. We propose that such predefined hyperstable β‐hairpins with recognition motifs are useful versatile tools for developing peptide‐based catalysts, and in biomarker design.

金属是蛋白质生物化学中的重要分子，因为它们参与各种基本的生物化学过程。受金属结合蛋白配位化学的启发，为了提高识别基序的稳定性，我们设计了具有特定金属结合裂缝的超稳定缝合β发夹。我们通过在长链16残基β发夹支架中建立Trp-Trp共价交联，并结合立体特异性Cys2‐His2四分体作为金属结合缝隙来实现这一点。这种水溶性肽显示出广泛的金属结合特性，具有Cu2+特异性。Cys-His四分体在金属离子选择性中的重要性通过Asp/Glu取代来确定。我们提出，这种具有识别基序的预定义超稳定β发夹是开发肽基催化剂和生物标志物设计的有用的通用工具。

引用次数: 0

Self‐assembly of thiolated versus non‐thiolated peptide amphiphiles 巯基化与非巯基化肽两亲物的自组装

IF 2.4 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptide Science

Pub Date : 2021-07-15 DOI: 10.1002/pep2.24236

E. A. Egorova, G. Gooris, Prianka Luther, J. Bouwstra, A. Kros, A. Boyle

The self‐assembly properties of peptide amphiphiles make them attractive for a range of applications, such as scaffolds for cell culture, drug delivery vehicles, or as stabilizing coatings for nanoparticles. The latter application requires derivatization of the amphiphiles to enable them to bind to, and interact with, a surface. This can be achieved by introduction of a thiol which facilitates binding to gold surfaces for example. However, small changes to the composition of peptide amphiphiles can have a large impact on their self‐assembly behavior. Therefore, we have synthesized and characterized a range of amphiphiles with different peptide sequences, alkyl chain lengths, and with or without a terminal thiol. We have characterized their structure and self‐assembly using circular dichroism (CD) spectroscopy, attenuated total reflection infrared (ATR‐IR) spectroscopy, and transmission electron microscopy (TEM). We discuss how changes to the peptide sequence and alkyl chain affect self‐assembly and compare the self‐assembly properties of thiolated and non‐thiolated amphiphiles. Such knowledge not only provides fundamental insights as to how self‐assembly can be controlled, but will also be helpful in determining which amphiphiles are most suitable for use as stabilizing nanoparticle coatings.

肽两亲物的自组装特性使其在一系列应用中具有吸引力，如细胞培养的支架、药物递送载体或纳米颗粒的稳定涂层。后一种应用需要两亲物的衍生化，使它们能够与表面结合并相互作用。这可以通过引入硫醇来实现，例如硫醇促进与金表面的结合。然而，肽两亲物组成的微小变化会对其自组装行为产生很大影响。因此，我们合成并表征了一系列具有不同肽序列、烷基链长度以及具有或不具有末端硫醇的两亲物。我们使用圆二色性（CD）光谱、衰减全反射红外光谱和透射电子显微镜（TEM）对它们的结构和自组装进行了表征。我们讨论了肽序列和烷基链的变化如何影响自组装，并比较了巯基化和非巯基化两亲物的自组装特性。这些知识不仅为如何控制自组装提供了基本的见解，而且有助于确定哪些两亲物最适合用作稳定纳米颗粒涂层。

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引用次数: 0

Synthesis and structure‐activity relationship of mitochondria‐targeting peptoids with varying hydrophobicity and cationic charge 具有不同疏水性和阳离子电荷的线粒体靶向类肽的合成及其构效关系

IF 2.4 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptide Science

Pub Date : 2021-07-14 DOI: 10.1002/pep2.24239

Soyoung Kim, Ji-Yu Lee, Jieun Choi, H. Nam, Jiwon Seo, Jiyoun Lee

Mitochondria‐targeted delivery methods offer a straightforward approach for studying mitochondria‐related diseases and potentially streamlining therapeutic development. Peptoids (oligo‐N‐substituted glycines) are biocompatible peptidomimetics that display similar physicochemical properties as peptides with the added advantage of enhanced resistance to proteolytic cleavage. In particular, amphipathic peptoids are membrane‐permeable and their cationic charges and hydrophobicity can be readily modified for specific purposes, such as cell penetration, anti‐cancer or antibacterial activity. Previously, we identified a series of amphipathic peptoids that showed efficient cell penetration and mitochondrial localization. As a continued effort to identify selective mitochondrial transporters, we designed new analogs with varying hydrophobicity and net charges. We observed that overall increase in hydrophobicity did not result in enhanced mitochondrial localization while maintaining high cell permeability. Moreover, a certain degree of a positive net charge was critical for mitochondrial localization. In conclusion, our mitochondria‐targeting peptoids provide a highly selective and robust delivery system for bioactive molecules.

线粒体靶向递送方法为研究线粒体相关疾病和潜在的简化治疗开发提供了一种直接的方法。类肽(oligo‐N‐取代的甘氨酸)是生物相容性的类肽，具有与肽相似的物理化学性质，并且具有增强的抗蛋白水解裂解能力的优势。特别是，两亲性肽类具有膜渗透性，它们的阳离子电荷和疏水性可以很容易地用于特定目的，如细胞渗透、抗癌或抗菌活性。在此之前，我们发现了一系列具有两亲性的类肽，它们显示出有效的细胞穿透和线粒体定位。作为鉴定选择性线粒体转运体的持续努力，我们设计了具有不同疏水性和净电荷的新类似物。我们观察到疏水性的总体增加并没有导致线粒体定位的增强，同时保持高细胞通透性。此外，一定程度的正电荷对线粒体定位至关重要。总之，我们的线粒体靶向类肽为生物活性分子提供了高选择性和强大的递送系统。

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引用次数: 3

Issue Information 问题信息

IF 2.4 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptide Science

Pub Date : 2021-07-01 DOI: 10.1002/pep2.24238

引用次数: 0

Strategies to Attenuate the Competence Regulon in Streptococcus pneumoniae. 削弱肺炎链球菌能力调控的策略。

IF 2.4 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptide Science

Pub Date : 2021-07-01 Epub Date: 2021-02-04 DOI: 10.1002/pep2.24222

Muralikrishna Lella, Yftah Tal-Gan

Streptococcus pneumoniae is an opportunistic respiratory human pathogen that poses a continuing threat to human health. Natural competence for genetic transformation in S. pneumoniae plays an important role in aiding pathogenicity and it is the best-characterized feature to acquire antimicrobial resistance genes by a frequent process of recombination. In S. pneumoniae, competence, along with virulence factor production, is controlled by a cell-density communication mechanism termed the competence regulon. In this review, we present the recent advances in the development of alternative methods to attenuate the pathogenicity of S. pneumoniae by targeting the various stages of the non-essential competence regulon communication system. We mainly focus on new developments related to competitively intercepting the competence regulon signaling through the introduction of promising dominant-negative Competence Stimulating Peptide (dnCSP) scaffolds. We also discuss recent reports on antibiotics that can block CSP export by disturbing the proton motive force (PMF) across the membrane and various ways to control the pneumococcal pathogenicity by activating the counter signaling circuit and targeting the pneumococcal proteome.

肺炎链球菌是一种机会性呼吸道人类病原体，对人类健康构成持续威胁。肺炎链球菌遗传转化的天然能力在辅助致病性方面起着重要作用，通过频繁的重组过程获得抗微生物抗性基因是其最好的特征。在肺炎链球菌中，能力和毒力因子的产生是由一种称为能力调节子的细胞密度通讯机制控制的。在这篇综述中，我们介绍了通过靶向非必需能力调节子通讯系统的各个阶段来减弱肺炎链球菌致病性的替代方法的最新进展。我们主要关注通过引入有前景的显性负性能力刺激肽（dnCSP）支架来竞争性阻断能力调节子信号传导的新进展。我们还讨论了最近关于抗生素的报道，这些抗生素可以通过干扰膜上的质子原动力（PMF）来阻断CSP的输出，以及通过激活反信号回路和靶向肺炎球菌蛋白质组来控制肺炎球菌致病性的各种方法。

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引用次数: 6

Stapled ACE2 peptidomimetics designed to target the SARS-CoV-2 spike protein do not prevent virus internalization. 设计靶向SARS-CoV-2刺突蛋白的钉接ACE2肽拟物不能阻止病毒内化。

IF 1.5 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptide Science

Pub Date : 2021-07-01 Epub Date: 2021-01-08 DOI: 10.1002/pep2.24217

Danielle C Morgan, Caroline Morris, Amit Mahindra, Connor M Blair, Gonzalo Tejeda, Imogen Herbert, Matthew L Turnbull, Gauthier Lieber, Brian J Willett, Nicola Logan, Brian Smith, Andrew B Tobin, David Bhella, George Baillie, Andrew G Jamieson

COVID-19 is caused by a novel coronavirus called severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). Virus cell entry is mediated through a protein-protein interaction (PPI) between the SARS-CoV-2 spike protein and angiotensin-converting enzyme 2 (ACE2). A series of stapled peptide ACE2 peptidomimetics based on the ACE2 interaction motif were designed to bind the coronavirus S-protein RBD and inhibit binding to the human ACE2 receptor. The peptidomimetics were assessed for antiviral activity in an array of assays including a neutralization pseudovirus assay, immunofluorescence (IF) assay and in-vitro fluorescence polarization (FP) assay. However, none of the peptidomimetics showed activity in these assays, suggesting that an enhanced binding interface is required to outcompete ACE2 for S-protein RBD binding and prevent virus internalization.

新冠肺炎是由一种称为严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）的新型冠状病毒引起的。病毒细胞进入是通过严重急性呼吸系统综合征冠状病毒2型刺突蛋白和血管紧张素转换酶2（ACE2）之间的蛋白质-蛋白质相互作用（PPI）介导的。设计了一系列基于ACE2相互作用基序的缝合肽ACE2肽模拟物，以结合冠状病毒S蛋白RBD并抑制与人类ACE2受体的结合。在一系列测定中评估肽模拟物的抗病毒活性，包括中和假病毒测定、免疫荧光（IF）测定和体外荧光偏振（FP）测定。然而，在这些测定中，没有一种肽模拟物显示出活性，这表明需要增强的结合界面才能在S蛋白RBD结合方面胜过ACE2并防止病毒内化。

引用次数: 0

Recent advances in protein modifications techniques for the targeting N‐terminal cysteine 靶向N端半胱氨酸蛋白修饰技术的最新进展

IF 2.4 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptide Science

Pub Date : 2021-06-11 DOI: 10.1002/pep2.24235

Nicholas Asiimwe, Mohammad Faysal Al Mazid, Dhiraj P. Murale, Y. Kim, Jun‐Seok Lee

N‐terminal modifications of proteins have garnered the attention of chemical biologists because of their critical roles in numerous cellular processes, including protein translocation, protein structural and metabolic stability, and the regulation of the half‐life of proteins by a process known as “N‐end rule pathway.” In addition, other posttranslational modification processes also depend on the N‐terminal signal sequences. Chemical probes are powerful tools that can be used to investigate N‐terminal modifications, to gain structural and functional insights into protein modification, protein‐protein interactions, protein localization, and protein dynamics. Most modifications target cysteine and lysine residues because of their high nucleophilicity. However, due to multiple occurrences of these residues in a protein at a given time, regioselective labeling can be quite difficult to accomplish. N‐terminal cysteine presents itself as a unique practical option to overcome regioselectivity and site‐specificity challenges. This review provides an overview of N‐terminal cysteine labeling tools, including N‐terminal cysteine condensation with aldehydes, cyanobenzothiazoles, cyclopropenones, and trans‐thioesterification. The review also highlights the technical challenges of each of the techniques, which need to be addressed to broaden the scope of these approaches.

蛋白质的N末端修饰引起了化学生物学家的注意，因为它们在许多细胞过程中发挥着关键作用，包括蛋白质易位、蛋白质结构和代谢稳定性，以及通过一种称为“N末端规则途径”的过程调节蛋白质的半衰期。此外，其他翻译后修饰过程也依赖于N端信号序列。化学探针是一种强大的工具，可用于研究N末端修饰，获得对蛋白质修饰、蛋白质相互作用、蛋白质定位和蛋白质动力学的结构和功能见解。大多数修饰针对半胱氨酸和赖氨酸残基，因为它们具有高亲核性。然而，由于这些残基在给定时间多次出现在蛋白质中，区域选择性标记可能很难实现。N末端半胱氨酸是克服区域选择性和位点特异性挑战的一种独特的实用选择。这篇综述概述了N-末端半胱氨酸标记工具，包括N-末端半胱氨酸与醛、氰基苯并噻唑、环丙烯酮和反式硫酯化的缩合。审查还强调了每种技术的技术挑战，需要解决这些挑战，以扩大这些方法的范围。

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引用次数: 13

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