Leader, B., Baca, Q. J. & Golan, D. E. Protein therapeutics: a summary and pharmacological classification. Nature Rev. Drug Discov. 7, 21-39

Department of Emergency Medicine, Brown Medical School, 593 Eddy Street, Providence, Rhode Island 02093, USA.
Nature Reviews Drug Discovery (Impact Factor: 41.91). 02/2008; 7(1):21-39. DOI: 10.1038/nrd2399
Source: PubMed


Once a rarely used subset of medical treatments, protein therapeutics have increased dramatically in number and frequency of use since the introduction of the first recombinant protein therapeutic--human insulin--25 years ago. Protein therapeutics already have a significant role in almost every field of medicine, but this role is still only in its infancy. This article overviews some of the key characteristics of protein therapeutics, summarizes the more than 130 protein therapeutics used currently and suggests a new classification of these proteins according to their pharmacological action.

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    • "Consumption of pangolins is driven by the folklore belief of their health benefits. However, pangolin scales consist of keratin, which has no proven pharmacological effects (Leader et al., 2008). "
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    ABSTRACT: Despite being protected by both international and national regulations, pangolins are threatened by illegal trade. Here we report mitochondrial DNA identification and haplotype richness estimation, using 239 pangolin scale samples from two confiscations in Hong Kong. We found a total of 13 genetically distinct cytochrome c oxidase I (COI) haplotypes in two confiscations (13 and ten haplotypes respectively, with ten shared haplotypes between confiscations). These haplotypes clustered in two distinct clades with one clade representing the Sunda pangolin (Manis javanica). The other clade did not match with any known Asian pangolin sequences, and likely represented a cryptic pangolin lineage in Asia. By fitting sample coverage and rarefaction/regression models to our sample data, we predicted that the total number of COI haplotypes in two confiscations were 14.86 and 11.06 respectively, suggesting that our sampling caught the majority of haplotypes and that we had adequately characterized each confiscation. We detected substantial sequence divergence among the seized scales, likely evidencing that the Sunda pangolins were harvested over wide geographical areas across Southeast Asia. Our study illustrates the value of applying DNA forensics for illegal wildlife trade monitoring.
    Full-text · Article · Jul 2015 · Global Ecology and Conservation
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    • "While the use of biologics to target PPIs is an interesting topic, we have chosen to limit the scope of this review to small molecules, peptides, and peptide mimics. For a thorough discussion on the subject of biologics, we refer the reader to other reviews (Leader et al., 2008; Sathish et al., 2013). However, it is worth nothing that many of the advantages and many of the challenges relevant to developing small-molecule inhibitors of PPIs are also relevant to the development of biologics. "
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    ABSTRACT: Protein-protein interactions (PPIs) underlie the majority of biological processes, signaling, and disease. Approaches to modulate PPIs with small molecules have therefore attracted increasing interest over the past decade. However, there are a number of challenges inherent in developing small-molecule PPI inhibitors that have prevented these approaches from reaching their full potential. From target validation to small-molecule screening and lead optimization, identifying therapeutically relevant PPIs that can be successfully modulated by small molecules is not a simple task. Following the recent review by Arkin et al., which summarized the lessons learnt from prior successes, we focus in this article on the specific challenges of developing PPI inhibitors and detail the recent advances in chemistry, biology, and computation that facilitate overcoming them. We conclude by providing a perspective on the field and outlining four innovations that we see as key enabling steps for successful development of small-molecule inhibitors targeting PPIs. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Full-text · Article · Jun 2015 · Chemistry & biology
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    • "Considering their effects on translation, SINEUPs may definitely find applications in protein manufacturing. More than 130 therapeutic proteins are currently in use and many more are under development, including antibodies (Leader et al., 2008; Matasci et al., 2008). Most production strategies have concentrated efforts in optimizing culture conditions and transcription of recombinant genes leaving room for improvement at post-transcriptional level (Lai et al., 2013). "
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    ABSTRACT: Whenever the function of a recombinant protein depends on post-translational processing, mammalian cells become an indispensable tool for their production. This is particularly true for biologics and therapeutic monoclonal antibodies (MAbs). Despite some drawbacks, Chinese Hamster Ovary (CHO) cells are the workhorse for MAbs production in academia and industry. Several methodologies have been adopted to improve expression and stability, including methods based on selective pressure or cell engineering. We have previously identified SINEUPs as a new functional class of natural and synthetic long non-coding RNAs that through the activity of an inverted SINEB2 element are able to promote translation of partially overlapping sense coding mRNAs. Here we show that by taking advantage of their modular structure, synthetic SINEUPs can be designed to increase production of secreted proteins. Furthermore, by experimentally validating antisense to elastin (AS-eln) RNA as a natural SINEUP, we show that SINEUP-mediated control may target extracellular proteins. These results lead us to propose synthetic SINEUPs as new versatile tools to optimize production of secreted proteins in manufacturing pipelines and natural SINEUPs as new regulatory RNAs in the secretory pathways. Copyright © 2015. Published by Elsevier B.V.
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