Recent Advances in the Research and Development of Alpha-1 Proteinase Inhibitor for Therapeutic Use

Karnaukhova, Elena

doi:10.5772/32547

Cited by 5 publications

(3 citation statements)

References 132 publications

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“…Expression in bacteria and yeast is inexpensive and particularly robust, achieving yields of several mg/L up to 1 g/L . Optimizing the expression of recombinant α 1 ‐AT remains a major area of study, as current replacement therapy is dependent on expensive plasma‐derived α 1 ‐AT …”

Section: Introductionmentioning

confidence: 99%

“…21,22 Optimizing the expression of recombinant α 1 -AT remains a major area of study, as current replacement therapy is dependent on expensive plasma-derived α 1 -AT. 23 Beyond replacement therapy, α 1 -AT has been investigated as a protein therapeutic for many other diseases including diabetes, graft-versus-host disease, cystic fibrosis, and arthritis among others. 24,25 This versatility stems from α 1 -AT's ability to inhibit several proteinases tied to inflammation, including neutrophil elastase as well as proteinase 3, 26 cathepsin G, 27 and several caspases which are cysteine proteinases.…”

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confidence: 99%

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Engineering the serpin α₁‐antitrypsin: A diversity of goals and techniques

Scott

Sheffield

2019

Protein Science

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α1‐Antitrypsin (α1‐AT) serves as an archetypal example for the serine proteinase inhibitor (serpin) protein family and has been used as a scaffold for protein engineering for >35 years. Techniques used to engineer α1‐AT include targeted mutagenesis, protein fusions, phage display, glycoengineering, and consensus protein design. The goals of engineering have also been diverse, ranging from understanding serpin structure–function relationships, to the design of more potent or more specific proteinase inhibitors with potential therapeutic relevance. Here we summarize the history of these protein engineering efforts, describing the techniques applied to engineer α1‐AT, specific mutants of interest, and providing an appended catalog of the >200 α1‐AT mutants published to date.

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

Engineering the serpin α₁‐antitrypsin: A diversity of goals and techniques

Scott

Sheffield

2019

Protein Science

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“…Alpha-1 antitrypsin (AAT), the archetype member of the serine proteinase inhibitor (SERPIN) super family, is a major circulating and tissue inhibitor of serine proteases [1]. AAT is predominantly synthesized by the liver and released into the circulation where it inhibits a variety of serine proteases.…”

Section: Introductionmentioning

confidence: 99%

Functional analysis of novel alpha-1 antitrypsin variants G320R and V321F

et al. 2014

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Alpha-1 antitrypsin (AAT) gene is highly polymorphic, with a large number of rare variants whose phenotypic consequences often remain inconclusive. Studies addressing functional characteristics of AAT variants are of significant biomedical importance since deficiency and dysfunctionality of AAT are associated with liver and lung diseases. We report the results of the functional analysis of two naturally occurring AAT variants, G320R and V321F, previously identified in patients with lung disease. Neither of variants has been fully functionally characterized. In order to perform their functional analysis both variants were expressed in prokaryotic and eukaryotic systems and their intracellular localization, activity, stability, and polymerization were determined. The results of this study demonstrated that variants G320R and V321F have neither impaired activity against porcine pancreatic elastase nor propensity to form polymers. However, both variants had altered electrophoretic mobility and reduced thermostability when compared to M variant of the protein, indicating a slightly impaired secondary or tertiary structure.

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