Evidence map›Paper›PMID 26144864›Full record

ArticleScientific reports2015

Balancing the Expression and Production of a Heterodimeric Protein: Recombinant Agkisacutacin as a Novel Antithrombotic Drug Candidate.

Yugang Guo, Jing Wu, Hao Jia, Wei Chen, Changsheng Shao, Lei Zhao, Jiajia Ma, Rui Li, Yongjun Zhong, Fang Fang and 8 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Urokinase-loaded cyclic RGD-decorated liposome targeted therapy forFrontiers in bioengineering and biotechnology · 2022
    Article
  6. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 4 institutions in 1 country.

Yugang Guo1] The CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Sciences, University of Science and Technology of China, Hefei, China [2] Hefei National Laboratory for Physical Sciences at Microscale, Engineering Technology Research Center of Biotechnology Drugs, Anhui Province, University of Science and Technology of China, Hefei, China [3] Anhui Engineering Research Center of Recombinant Protein Pharmaceutical Biotechnology, Institute of advanced technology, University of Science and Technology of China, Hefei, China.
Jing Wu1] Hefei National Laboratory for Physical Sciences at Microscale, Engineering Technology Research Center of Biotechnology Drugs, Anhui Province, University of Science and Technology of China, Hefei, China [2] Anhui Engineering Research Center of Recombinant Protein Pharmaceutical Biotechnology, Institute of advanced technology, University of Science and Technology of China, Hefei, China.
Hao JiaThe CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Sciences, University of Science and Technology of China, Hefei, China.
Wei Chen1] Hefei National Laboratory for Physical Sciences at Microscale, Engineering Technology Research Center of Biotechnology Drugs, Anhui Province, University of Science and Technology of China, Hefei, China [2] Anhui Engineering Research Center of Recombinant Protein Pharmaceutical Biotechnology, Institute of advanced technology, University of Science and Technology of China, Hefei, China.
Changsheng Shao1] Hefei National Laboratory for Physical Sciences at Microscale, Engineering Technology Research Center of Biotechnology Drugs, Anhui Province, University of Science and Technology of China, Hefei, China [2] Anhui Engineering Research Center of Recombinant Protein Pharmaceutical Biotechnology, Institute of advanced technology, University of Science and Technology of China, Hefei, China.
Lei Zhao1] Hefei National Laboratory for Physical Sciences at Microscale, Engineering Technology Research Center of Biotechnology Drugs, Anhui Province, University of Science and Technology of China, Hefei, China [2] Anhui Engineering Research Center of Recombinant Protein Pharmaceutical Biotechnology, Institute of advanced technology, University of Science and Technology of China, Hefei, China.
Jiajia Ma1] The CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Sciences, University of Science and Technology of China, Hefei, China [2] Hefei National Laboratory for Physical Sciences at Microscale, Engineering Technology Research Center of Biotechnology Drugs, Anhui Province, University of Science and Technology of China, Hefei, China [3] Anhui Engineering Research Center of Recombinant Protein Pharmaceutical Biotechnology, Institute of advanced technology, University of Science and Technology of China, Hefei, China.
Rui LiThe CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Sciences, University of Science and Technology of China, Hefei, China.
Yongjun ZhongThe CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Sciences, University of Science and Technology of China, Hefei, China.
Fang FangThe CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Sciences, University of Science and Technology of China, Hefei, China.
Dong WangThe CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Sciences, University of Science and Technology of China, Hefei, China.
Jie Sun1] The CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Sciences, University of Science and Technology of China, Hefei, China [2] Hefei National Laboratory for Physical Sciences at Microscale, Engineering Technology Research Center of Biotechnology Drugs, Anhui Province, University of Science and Technology of China, Hefei, China [3] Anhui Engineering Research Center of Recombinant Protein Pharmaceutical Biotechnology, Institute of advanced technology, University of Science and Technology of China, Hefei, China.
Fang QianZhaoke Pharmaceutical (Hefei) Co. Ltd., Hefei, Anhui, China.
Xiangrong DaiZhaoke Pharmaceutical (Hefei) Co. Ltd., Hefei, Anhui, China.
Guohui ZhangZhaoke Pharmaceutical (Hefei) Co. Ltd., Hefei, Anhui, China.
Zhigang Tian1] The CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Sciences, University of Science and Technology of China, Hefei, China [2] Hefei National Laboratory for Physical Sciences at Microscale, Engineering Technology Research Center of Biotechnology Drugs, Anhui Province, University of Science and Technology of China, Hefei, China [3] Anhui Engineering Research Center of Recombinant Protein Pharmaceutical Biotechnology, Institute of advanced technology, University of Science and Technology of China, Hefei, China.
Benjamin Xiaoyi LiLee's Pharmaceutical Holdings Limited, Shatin, Hong Kong, China.
Weihua Xiao1] The CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Sciences, University of Science and Technology of China, Hefei, China [2] Hefei National Laboratory for Physical Sciences at Microscale, Engineering Technology Research Center of Biotechnology Drugs, Anhui Province, University of Science and Technology of China, Hefei, China [3] Anhui Engineering Research Center of Recombinant Protein Pharmaceutical Biotechnology, Institute of advanced technology, University of Science and Technology of China, Hefei, China.
University of Science and Technology of China · CNBeike Biotechnology (China) · CNHefei National Center for Physical Sciences at Nanoscale · CNLee's Pharmaceutical (China) · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Agkisacucetin extracted from the venom of Agkistrodon acutus has been demonstrated to be a promising antithrombotic drug candidate in clinical studies due to its function as a novel platelet membrane glycoprotein (GP) Ib inhibitor. Agkisacucetin is a heterodimeric protein composed of α- and β-subunits with seven disulphide bonds. Both subunits form inactive homodimeric products, which cause difficulties for recombinant production. In this study, Agkisacucetin α- and β-subunits were inserted sequentially into the chromosome of Pichia pastoris at the mutant histidinol dehydrogenase gene and ribosomal DNA repeat sites, respectively. By optimizing the gene copies and productivity of each subunit by drug screening, we successfully obtained a recombinant strain with balanced expression of the two subunits. Using this strain, a yield greater than 100 mg/L recombinant Agkisacucetin in fed-batch fermentation was reached. The recombinant Agkisacucetin possessed extremely similar binding affinity to recombinant GPIb and human platelets in in vitro assays, and its ristocetin-induced platelet aggregation activity ex vivo was identical to that of the extracted native Agkisacucetin, demonstrating that the yeast-derived Agkisacucetin could be an effective alternative to native Agkisacucetin. Moreover, this study provides an effective strategy for balancing the expression and production of heterodimeric proteins in P. pastoris.

Indexed as

AgkistrodonAmino Acid SequenceAnimalsAntineoplastic AgentsBatch Cell Culture TechniquesCrotalid VenomsDimerizationHumansMolecular Sequence DataPichiaPlasmidsPlatelet AggregationPlatelet Glycoprotein GPIb-IX ComplexProtein BindingProtein SubunitsRecombinant ProteinsagkisacutacinAntineoplastic AgentsCrotalid VenomsPlatelet Glycoprotein GPIb-IX ComplexProtein SubunitsRecombinant ProteinsRistocetin

Identifiers

PMID26144864
PMCPMC4491848
OpenAlexW2264146102

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.