Protein Engineering Design & Selection最新文献_第8页

Engineering stable carbonic anhydrases for CO2 capture: a critical review. 工程稳定的碳酸酐酶用于二氧化碳捕获:一个重要的回顾。

IF 2.4 4区生物学

Protein Engineering Design & Selection Pub Date : 2021-02-15 DOI: 10.1093/protein/gzab021

Mirfath Sultana Mesbahuddin, Aravindhan Ganesan, Subha Kalyaanamoorthy

引用次数: 7

A versatile assay platform for enzymatic poly(ethylene-terephthalate) degradation. 一个通用的酶促聚对苯二甲酸乙酯降解测定平台。

IF 2.4 4区生物学

Protein Engineering Design & Selection Pub Date : 2021-02-15 DOI: 10.1093/protein/gzab022

Sebastian Weigert, Andreas Gagsteiger, Teresa Menzel, Birte Höcker

引用次数: 3

Rational engineering of an erythropoietin fusion protein to treat hypoxia. 合理设计促红细胞生成素融合蛋白治疗缺氧。

IF 2.4 4区生物学

Protein Engineering Design & Selection Pub Date : 2021-02-15 DOI: 10.1093/protein/gzab025

Jungmin Lee, Andyna Vernet, Nathalie G Gruber, Kasia M Kready, Devin R Burrill, Jeffrey C Way, Pamela A Silver

{"title":"Rational engineering of an erythropoietin fusion protein to treat hypoxia.","authors":"Jungmin Lee, Andyna Vernet, Nathalie G Gruber, Kasia M Kready, Devin R Burrill, Jeffrey C Way, Pamela A Silver","doi":"10.1093/protein/gzab025","DOIUrl":"https://doi.org/10.1093/protein/gzab025","url":null,"abstract":"Erythropoietin enhances oxygen delivery and reduces hypoxia-induced cell death, but its pro-thrombotic activity is problematic for use of erythropoietin in treating hypoxia. We constructed a fusion protein that stimulates red blood cell production and neuroprotection without triggering platelet production, a marker for thrombosis. The protein consists of an anti-glycophorin A nanobody and an erythropoietin mutant (L108A). The mutation reduces activation of erythropoietin receptor homodimers that induce erythropoiesis and thrombosis, but maintains the tissue-protective signaling. The binding of the nanobody element to glycophorin A rescues homodimeric erythropoietin receptor activation on red blood cell precursors. In a cell proliferation assay, the fusion protein is active at 10-14 M, allowing an estimate of the number of receptor-ligand complexes needed for signaling. This fusion protein stimulates erythroid cell proliferation in vitro and in mice, and shows neuroprotective activity in vitro. Our erythropoietin fusion protein presents a novel molecule for treating hypoxia.","PeriodicalId":54543,"journal":{"name":"Protein Engineering Design & Selection","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2021-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39835737","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

High-efficacy, high-manufacturability human VH domain antibody therapeutics from transgenic sources. 来自转基因来源的高效、高可制造性人VH结构域抗体疗法。

IF 2.4 4区生物学

Protein Engineering Design & Selection Pub Date : 2021-02-15 DOI: 10.1093/protein/gzab012

Kasandra Bélanger, Jamshid Tanha

{"title":"High-efficacy, high-manufacturability human VH domain antibody therapeutics from transgenic sources.","authors":"Kasandra Bélanger, Jamshid Tanha","doi":"10.1093/protein/gzab012","DOIUrl":"https://doi.org/10.1093/protein/gzab012","url":null,"abstract":"Interest in single-domain antibodies (sdAbs) stems from their unique structural/pronounced, hence therapeutically desirable, features. From the outset-as therapeutic modalities-human antibody heavy chain variable domains (VHs) attracted a particular attention compared with 'naturally-occurring' camelid and shark heavy-chain-only antibody variable domains (VHHs and VNARs, respectively) due to their perceived lack of immunogenicity. However, they have not quite lived up to their initial promise as the VH hits, primarily mined from synthetic VH phage display libraries, have too often been plagued with aggregation tendencies, low solubility and low affinity. Largely unexplored, synthetic camelized human VH display libraries appeared to have remediated the aggregation problem, but the low affinity of the VH hits still persisted, requiring undertaking additional, laborious affinity maturation steps to render VHs therapeutically feasible. A wholesome resolution has recently emerged with the development of non-canonical transgenic rodent antibody discovery platforms that appear to facilely and profusely generate high affinity, high solubility and aggregation-resistant human VHs.","PeriodicalId":54543,"journal":{"name":"Protein Engineering Design & Selection","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2021-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/protein/gzab012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38914156","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: 2

Recent developments in engineering protein-protein interactions using phage display. 利用噬菌体展示技术工程蛋白-蛋白相互作用的最新进展。

IF 2.4 4区生物学

Protein Engineering Design & Selection Pub Date : 2021-02-15 DOI: 10.1093/protein/gzab014

Chen T Liang, Olivia M A Roscow, Wei Zhang

引用次数: 5

Improvement of Moloney murine leukemia virus reverse transcriptase thermostability by introducing a disulfide bridge in the ribonuclease H region. 在核糖核酸酶H区引入二硫桥改善Moloney小鼠白血病病毒逆转录酶的热稳定性。

IF 2.4 4区生物学

Protein Engineering Design & Selection Pub Date : 2021-02-15 DOI: 10.1093/protein/gzab006

Yutaro Narukawa, Mako Kandabashi, Tongyang Li, Misato Baba, Haruka Hara, Kenji Kojima, Kei Iida, Takayoshi Hiyama, Sho Yokoe, Tomomi Yamazaki, Teisuke Takita, Kiyoshi Yasukawa

引用次数: 2

The evolution and engineering of enzyme activity through tuning conformational landscapes. 通过调整构象景观的酶活性的进化和工程。

IF 2.4 4区生物学

Protein Engineering Design & Selection Pub Date : 2021-02-15 DOI: 10.1093/protein/gzab009

Adam M Damry, Colin J Jackson

引用次数: 7

Evolution of β-lactamases and enzyme promiscuity. β-内酰胺酶的进化与酶的混杂性。

IF 2.4 4区生物学

Protein Engineering Design & Selection Pub Date : 2021-02-15 DOI: 10.1093/protein/gzab013

Christopher Fröhlich, John Z Chen, Sevan Gholipour, Ayse N Erdogan, Nobuhiko Tokuriki

引用次数: 11

Protease-stable DARPins as promising oral therapeutics. 蛋白酶稳定的DARPins作为有前途的口服治疗药物。

IF 2.6 4区生物学

Protein Engineering Design & Selection Pub Date : 2021-02-15 DOI: 10.1093/protein/gzab028

Rudo A Simeon, Yu Zeng, Vikas Chonira, Andrea Martinez Aguirre, Mauricio Lasagna, Marko Baloh, Joseph A Sorg, Cecilia Tommos, Zhilei Chen

{"title":"Protease-stable DARPins as promising oral therapeutics.","authors":"Rudo A Simeon, Yu Zeng, Vikas Chonira, Andrea Martinez Aguirre, Mauricio Lasagna, Marko Baloh, Joseph A Sorg, Cecilia Tommos, Zhilei Chen","doi":"10.1093/protein/gzab028","DOIUrl":"10.1093/protein/gzab028","url":null,"abstract":"Clostridioides difficile is an enteric bacterium whose exotoxins, TcdA and TcdB, inactivate small GTPases within the host cells, leading to bloody diarrhea. In prior work, our group engineered a panel of potent TcdB-neutralizing designed ankyrin repeat proteins (DARPin) as oral therapeutics against C. difficile infection. However, all these DARPins are highly susceptible to digestion by gut-resident proteases, i.e. trypsin and chymotrypsin. Close evaluation of the protein sequence revealed a large abundance of positively charged and aromatic residues in the DARPin scaffold. In this study, we significantly improved the protease stability of one of the DARPins, 1.4E, via protein engineering. Unlike 1.4E, whose anti-TcdB EC50 increased >83-fold after 1-hour incubation with trypsin (1 mg/ml) or chymotrypsin (0.5 mg/ml), the best progenies-T10-2 and T10b-exhibit similar anti-TcdB potency as their parent in PBS regardless of protease treatment. The superior protease stability of T10-2 and T10b is attributed to the removal of nearly all positively charged and aromatic residues except those directly engaged in target binding. Furthermore, T10-2 was found to retain significant toxin-neutralization ability in ex vivo cecum fluid and can be easily detected in mouse fecal samples upon oral administration. Both T10-2 and T10b enjoy a high thermo- and chemo-stability and can be expressed very efficiently in Escherichia coli (>100 mg/l in shaker flasks). We believe that, in additional to their potential as oral therapeutics against C. difficile infection, T10-2 and T10b can also serve as a new generation DARPin scaffold with superior protease stability.","PeriodicalId":54543,"journal":{"name":"Protein Engineering Design & Selection","volume":"34 ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2021-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8861517/pdf/gzab028.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10431620","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

Molecular flexibility in computational protein design: an algorithmic perspective. 计算蛋白设计中的分子灵活性:一个算法的视角。

IF 2.4 4区生物学

Protein Engineering Design & Selection Pub Date : 2021-02-15 DOI: 10.1093/protein/gzab011

Younes Bouchiba, Juan Cortés, Thomas Schiex, Sophie Barbe

引用次数: 4