scholarly journals Size-based Degradation of Therapeutic Proteins - Mechanisms, Modelling and Control

2021 ◽  
Vol 12 (1) ◽  
pp. 68-84
Author(s):  
Rohit Bansal ◽  
Saurabh Kumar Jha ◽  
Niraj Kumar Jha
Keyword(s):  
Protein Degradation ◽  
Therapeutic Proteins ◽  
Protein Therapeutics ◽  
Degradation Pathways ◽  
High Demand ◽  
Fragmentation Pathways ◽  
Great Demand ◽  
And Control

Abstract Protein therapeutics are in great demand due to their effectiveness towards hard-to-treat diseases. Despite their high demand, these bio-therapeutics are very susceptible to degradation via aggregation, fragmentation, oxidation, and reduction, all of which are very likely to affect the quality and efficacy of the product. Mechanisms and modelling of these degradation (aggregation and fragmentation) pathways is critical for gaining a deeper understanding of stability of these products. This review aims to provide a summary of major developments that have occurred towards unravelling the mechanisms of size-based protein degradation (particularly aggregation and fragmentation), modelling of these size-based degradation pathways, and their control. Major caveats that remain in our understanding and control of size-based protein degradation have also been presented and discussed.

Protein Therapeutics: An Updated Review

2021 ◽  
Vol 11 (3) ◽  
pp. 253-257
Author(s):  
Arindam Chakraborty ◽  
Dipak Kumar Singha ◽  
Manas Chakraborty ◽  
Payel Mukherjee
Keyword(s):  
Stability Problem ◽  
Clinical Success ◽  
Treatment Options ◽  
Therapeutic Proteins ◽  
Protein Therapeutics ◽  
Therapeutic Protein ◽  
Recent Advancement ◽  
Pharmaceutical Industries ◽  
Day By Day ◽  
Pharmaceutical Biotechnology

Therapeutic protein are one of the prime option of biologicals as per their clinical uses. In recent times, uses of therapeutic protein increases day by day. Protein therapeutics are used extensively to treat various diseases like cancer, AIDS etc. Due to recent advancement in pharmaceutical biotechnology the interest towards therapeutic proteins are augmenting nowadays. Various clinical research are going on in this field to treat different diseases and pharmaceutical industries are also make interest on therapeutic proteins. Among the various treatment options therapeutic protein will provide highest chance of clinical success. Some recent clinical trials demonstrate that therapeutic protein may provide the safe and potential option to treat various diseases, but there are some drawbacks also like some immunogenic issues, safety, stability problem of protein, degradation of protein in various conditions.

scholarly journals The NMR Spectral Measurement Database: A System for Organizing and Accessing NMR Spectra of Therapeutic Proteins

2021 ◽  
Vol 126 ◽  
Author(s):  
Niksa Blonder ◽  
Frank Delaglio
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Spectral Data ◽  
Data Storage ◽  
Nmr Spectra ◽  
Therapeutic Proteins ◽  
Data Access ◽  
Protein Therapeutics ◽  
Spectral Measurement ◽  
Storage And Retrieval

The Nuclear Magnetic Resonance Spectral Measurement Database (NMR-SMDB) was developed for the purpose of organizing and searching NMR spectral data of protein therapeutics, linking spectra to corresponding sample information and enabling quick access to full datasets and entire studies. In addition to supporting internal research at the National Institute of Standards and Technology (NIST), the system could facilitate data access to stakeholders outside of NIST, and future versions of the database software itself could be installed by others for their own data storage and retrieval.

scholarly journals Inhibition of Protein Ubiquitination by Paraquat and 1-Methyl-4-Phenylpyridinium Impairs Ubiquitin-Dependent Protein Degradation Pathways

2015 ◽  
Vol 53 (8) ◽  
pp. 5229-5251 ◽  
Author(s):  
Juliana Navarro-Yepes ◽  
Annadurai Anandhan ◽  
Erin Bradley ◽  
Iryna Bohovych ◽  
Bo Yarabe ◽  
...  
Keyword(s):  
Protein Degradation ◽  
Degradation Pathways ◽  
Protein Ubiquitination ◽  
Dependent Protein

scholarly journals Heat shock inhibits and activates different protein degradation pathways and proteinase activities in Neurospora crassa

1994 ◽  
Vol 124 (2) ◽  
pp. 215-225 ◽  
Author(s):  
Saadat Mohsenzadeh ◽  
Cunshuan Xu ◽  
Franco Fracella ◽  
Ludger Rensing
Keyword(s):  
Heat Shock ◽  
Neurospora Crassa ◽  
Protein Degradation ◽  
Degradation Pathways

Endocrine and amino acid regulation of liver macroautophagy and proteolytic function

1994 ◽  
Vol 266 (1) ◽  
pp. G118-G122
Author(s):  
E. Bergamini ◽  
A. Del Roso ◽  
Z. Gori ◽  
P. Masiello ◽  
M. Masini ◽  
...  
Keyword(s):  
Amino Acids ◽  
Protein Degradation ◽  
Intraperitoneal Administration ◽  
Physiological Mechanism ◽  
Albino Rats ◽  
Sprague Dawley ◽  
Subsequent Increase ◽  
Stimulatory Agent ◽  
And Control

Regulation of liver macroautophagy and protein degradation by hormones and direct regulatory amino acids were studied in male 2-mo-old Sprague-Dawley albino rats with the use of the antilipolytic agent 3,5'-dimethylpyrazole (DMP; 12 mg/kg body wt ip) as a stimulatory agent. Injection of DMP decreased glutamine plasma levels and glutamine release from the perfused liver. Autophagic vacuoles were observed in the pericanalicular area of liver cells after 30 min. Levels and release of other regulatory amino acids did not exhibit any significant decrease but subsequently increased. Intraperitoneal administration of glutamine inhibited the proteolytic response. In conclusion, these studies demonstrate that in vivo induction and control of liver macroautophagy and protein degradation by the physiological mechanism (i.e., by shortage of nutrients) involve unbalanced and asynchronous changes in the levels of selected direct regulatory amino acids (i.e., a decrease in glutamine and a subsequent increase in leucine and tyrosine levels)

Ubiquilins in the crosstalk among proteolytic pathways

2012 ◽  
Vol 393 (6) ◽  
pp. 441-447 ◽  
Author(s):  
Dong Yun Lee ◽  
Eric J. Brown
Keyword(s):  
Protein Degradation ◽  
Binding Proteins ◽  
Major Protein ◽  
Degradation Pathways ◽  
Cytosolic Proteins ◽  
Sequestosome 1 ◽  
Ubiquitin Binding ◽  
Proteolytic Pathways

Abstract Protein degradation occurs through several distinct proteolytic pathways for membrane and cytosolic proteins. There is evidence that these processes are linked and that crosstalk among these major protein degradation pathways occurs. Ubiquilins, a family of ubiquitin-binding proteins, are involved in all protein degradation pathways. This minireview provides an overview of ubiquilin function in protein degradation and contrasts it with sequestosome-1 (p62), a protein that also has been implicated in multiple proteolytic pathways.

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