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IF 2.4 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-07-01 DOI: 10.1002/pep2.24278
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引用次数: 0
Development of Convergent Hybrid Phase Ligation for Efficient and Convenient Total Synthesis of Proteins. 开发用于高效便捷地全合成蛋白质的聚合混合相连接技术。
IF 1.5 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-07-01 Epub Date: 2023-05-25 DOI: 10.1002/pep2.24323
Ziyong Z Hong, Ruixuan R Yu, Xiaoyu Zhang, Allison M Webb, Nathaniel L Burge, Michael G Poirier, Jennifer J Ottesen

Simple and efficient total synthesis of homogeneous and chemically modified protein samples remains a significant challenge. Here, we report development of a convergent hybrid phase native chemical ligation (CHP-NCL) strategy for facile preparation of proteins. In this strategy, proteins are split into ~100-residue blocks, and each block is assembled on solid support from synthetically accessible peptide fragments before ligated together into full-length protein in solution. With the new method, we increase the yield of CENP-A synthesis by 2.5-fold compared to the previous hybrid phase ligation approach. We further extend the new strategy to the total chemical synthesis of 212-residue linker histone H1.2 in unmodified, phosphorylated, and citrullinated forms, each from eight peptide segments with only one single purification. We demonstrate that fully synthetic H1.2 replicates the binding interactions of linker histones to intact mononucleosomes, as a proxy for the essential function of linker histones in the formation and regulation of higher order chromatin structure.

简单高效地全合成均质和化学修饰的蛋白质样品仍然是一项重大挑战。在此,我们报告了一种用于便捷制备蛋白质的聚合杂化相原生化学连接(CHP-NCL)策略的发展情况。在这一策略中,蛋白质被分割成约 100 个残基的区块,每个区块由可合成的肽片段组装在固体支持物上,然后在溶液中连接成全长蛋白质。采用这种新方法,我们将 CENP-A 的合成产量比以前的杂交阶段连接方法提高了 2.5 倍。我们进一步将新策略扩展到 212 个残基连接体组蛋白 H1.2 的全化学合成,包括未修饰型、磷酸化型和瓜氨酸化型,每种组蛋白由八个肽段组成,只需一次纯化。我们证明,全合成的 H1.2 复制了连接组蛋白与完整的单核糖体的结合相互作用,这代表了连接组蛋白在高阶染色质结构的形成和调控中的重要功能。
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引用次数: 0
Controlled aggregation properties of threonine modified by protecting groups to unusual self‐assembled structures 保护基修饰苏氨酸的可控聚集特性
IF 2.4 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-06-22 DOI: 10.1002/pep2.24324
Nidhi Gour, Vivekshinh Kshtriya, B. Koshti, Monisha Patel, D. Boukhvalov
We report for the very first time the controlled structural changes in the self‐assemblies of N‐(9‐fluorenylmethoxycarbonyl)‐O‐tert‐butyl‐l‐threonine (Fmoc‐Thr(tBu)‐OH) (FTU) to well defined unique morphologies. The self‐assembling properties of FTU were very interesting and intriguing as it resulted in the formation of unusual structures which resembles fibrous dumbbells and double‐sided broomstick‐like morphologies along with conventional spheres and rods under controlled conditions of concentration and temperature. The self‐assembly of other derivatives of threonine as well as another hydroxyl containing amino acid with same modification that is, ((N‐(9H‐fluoren‐9‐yl)methoxy)carbonyl)‐O‐(tert‐butyl)‐l‐serine (Fmoc‐Ser(tBu)‐OH) (FSU) was also studied to understand the crucial role of –Fmoc, ‐tBu and an additional –CH3 group present in the structure of FTU in the process of self‐assembly. Solvent dependent morphological studies of FTU and FSU suggest important role of solubility parameters and crystallization in formation of these unusual structures. The control experiments of co‐incubation with tannic acid and urea and solution state 1H‐NMR studies elucidate π–π stacking interactions as the key driving force for the structure formation. Further, the interactions which can occur between pairs of FTU and FSU which cause initial self‐assembly was studied theoretically via computational modeling. These studies suggest pair of FTU can either interact via head‐to‐head (HH) or head‐to‐tail (HT) configurations and the most favorable probabilities of either of these interactions lead to morphological transitions in FTU self‐assembly under varying conditions. The studies reported herein hence demonstrate that bioorganic molecules like protected single amino acids can be efficiently used as scaffold for self‐assembly and provide a very simple and facile bottom‐up‐approach for the design of uncommon novel micro/nanoarchitects for multifarious applications.
我们首次报道了N-(9-芴甲氧羰基)-O-叔丁基-l-苏氨酸(Fmoc-Thr(tBu)-OH)(FTU)自组装过程中可控的结构变化,使其具有明确的独特形态。FTU的自组装性质非常有趣,因为它在控制浓度和温度的条件下形成了类似于纤维哑铃和双侧扫帚柄状形态以及传统球体和棒的不同寻常的结构。还研究了苏氨酸的其他衍生物以及另一种具有相同修饰的含羟基氨基酸((N-(9H-芴-9-基)甲氧基)羰基)-O-(叔丁基)-1-丝氨酸(Fmoc-Ser(tBu)-OH)(FSU)的自组装,以了解-Fmoc的关键作用,tBu和在自组装过程中FTU结构中存在的额外-CH3基团。FTU和FSU的溶剂依赖性形态研究表明,溶解度参数和结晶在这些不寻常结构的形成中起着重要作用。与单宁酸和尿素共孵育的对照实验以及溶液态1H-NMR研究表明,π–π堆积相互作用是结构形成的关键驱动力。此外,通过计算建模从理论上研究了FTU和FSU对之间可能发生的导致初始自组装的相互作用。这些研究表明,一对FTU可以通过头对头(HH)或头对头尾(HT)构型相互作用,并且在不同条件下,这两种相互作用的最有利概率都会导致FTU自组装的形态转变。因此,本文报道的研究表明,像受保护的单个氨基酸这样的生物有机分子可以有效地用作自组装的支架,并为设计用于各种应用的不常见的新型微/纳米建筑师提供了一种非常简单和方便的自下而上的方法。
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引用次数: 0
Issue Information 问题信息
IF 2.4 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-05-01 DOI: 10.1111/nous.12413
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引用次数: 0
Nanomole‐scale photochemical thiol‐ene chemistry for high‐throughput late‐stage diversification of peptide macrocycles 纳米级光化学硫醇烯化学用于肽大环的高通量后期多样化
IF 2.4 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-04-26 DOI: 10.1002/pep2.24310
M. Nolan, M. Schüttel, Eoin M. Scanlan, Alexander L. Nielsen
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引用次数: 0
Erratum: Current peptide vaccine and immunotherapy approaches against Alzheimer's disease 勘误表:目前针对阿尔茨海默病的肽疫苗和免疫疗法方法
IF 2.4 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-04-19 DOI: 10.1002/pep2.24309
In the published article cited above, there was an error at the start of paragraph five, section two, β-Amyloid peptide vaccines where ACI-24 is introduced: the company behind ACI-24 was mis-attributed. The first sentence of the paragraph originally read: ACI-24 (AC Immune, Roche and Genentech) is designed to avoid eliciting a Th-1 response to Aβ. The sentence should read: ACI-24 (AC Immune) is designed to avoid eliciting a Th-1 response to Aβ. There was also an error at the start of paragraph six, section two, β-Amyloid peptide vaccines where ABvac40 is introduced: the company behind ABvac40 was mis-attributed. The first sentence of the paragraph originally read: ABvac40 (Axon Neuroscience SE) is designed to target the C-terminus of Aβ1–40. The sentence should read: ABvac40 (Araclon Biotech) is designed to target the C-terminus of Aβ1–40. The authors apologise for any inconvenience this may have caused. DOI: 10.1002/pep2.24309
在上述发表的文章中,在第五段第二节β-淀粉样肽疫苗的开头出现了一个错误,其中引入了ACI-24:ACI-24背后的公司被错误地归因。该段的第一句话最初是:ACI-24(AC Immune、Roche和Genentech)旨在避免引发对aβ的Th-1反应。句子应为:ACI-24(AC免疫)旨在避免引发对aβ的Th-1反应。在引入ABvac40的第六段第二节β-淀粉样肽疫苗的开头也有一个错误:ABvac40背后的公司被错误归因。该段的第一句话最初是:ABvac40(Axon Neuroscience SE)旨在靶向Aβ1-40的C末端。句子应为:ABvac40(阿克隆生物技术公司)旨在靶向Aβ1-40的C末端。对于由此造成的不便,作者深表歉意。DOI:10.1002/ep2.24309
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引用次数: 0
Membrane permeability and antimicrobial peptides: Much more than just making a hole 膜渗透性和抗菌肽:不仅仅是打一个洞
IF 2.4 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-03-31 DOI: 10.1002/pep2.24305
J. C. Espeche, Romina Varas, P. Maturana, A. Cutró, P. Maffía, A. Hollmann
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引用次数: 1
Host defense peptides identified in human apolipoprotein B as natural food bio‐preservatives: Evaluation of their biosafety and digestibility 人载脂蛋白B中鉴定的宿主防御肽作为天然食品生物防腐剂:生物安全性和消化率评估
IF 2.4 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-03-29 DOI: 10.1002/pep2.24308
Eliana Dell’Olmo, Katia Pane, Martina Schibeci, Angela Cesaro, Maria G De Luca, Shurooq Ismail, R. Gaglione, Angela Arciello
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引用次数: 0
Fine‐tuning the antimicrobial activity of β‐hairpin peptides with fluorinated amino acids 用氟化氨基酸微调β -发夹肽的抗菌活性
IF 2.4 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-03-08 DOI: 10.1002/pep2.24306
S. Chowdhary, Tim Pelzer, Mareike Saathoff, Elisa Quaas, Johanna Pendl, M. Fulde, B. Koksch
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引用次数: 1
Guidelines for designing peptoid structures: Insights from the Peptoid Data Bank peptoid结构设计指南:peptoid数据库的见解
IF 2.4 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-03-08 DOI: 10.1002/pep2.24307
James R B Eastwood, Ethan I. Weisberg, Dana Katz, R. Zuckermann, K. Kirshenbaum
The number of structural studies of peptoids has grown dramatically over the past 20 years. To date, over 100 high‐resolution structures have been reported for peptoids, which are typically defined as N‐substituted glycine oligomers. We have collected these structures and standardized their sequence representations to facilitate structural analysis as the dataset continues to grow. These structures are presented online as The Peptoid Data Bank (databank.peptoids.org), which also provides persistent links to the published structural data. This review analyzes the present collection of structures and finds extensive support for grouping side chains by their chemistry at the position adjacent to the backbone nitrogen. Groups of side chains with similar chemistry at this position show similar influences on the conformational preferences of the backbone. We also observe a relationship between the side chain and backbone conformations for many monomers that has not previously attracted significant discussion: the values of the χ1 and ϕ dihedrals are correlated. We outline a general design strategy for attaining a specific backbone conformation based on the patterns seen in the collected structures.
在过去的20年里,类蛋白结构研究的数量急剧增加 年。到目前为止,已经报道了超过100种蛋白胨的高分辨率结构,其通常被定义为N取代的甘氨酸低聚物。随着数据集的不断增长,我们收集了这些结构并对其序列表示进行了标准化,以便于进行结构分析。这些结构在网上被称为Peptoid数据库(database.petoids.org),它还提供了到已发布结构数据的持久链接。这篇综述分析了目前的结构集合,并发现了通过侧链在与主链氮相邻的位置的化学性质对侧链进行分组的广泛支持。在该位置具有相似化学性质的侧链组对主链的构象偏好显示出相似的影响。我们还观察到许多单体的侧链和主链构象之间的关系,这种关系以前没有引起过重大讨论:χ1和ξ二面体的值是相关的。我们概述了一种通用的设计策略,用于基于在收集的结构中看到的模式来获得特定的骨架构象。
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引用次数: 4
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Peptide Science
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