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Sources of Essential Oils
Published in K. Hüsnü Can Başer, Gerhard Buchbauer, Handbook of Essential Oils, 2020
Chlodwig Franz, Johannes Novak
Protein engineering is the application of scientific methods (mathematical and laboratory methods) to develop useful or valuable proteins. There are two general strategies for protein engineering, random mutagenesis and rational design. In rational design, detailed knowledge of the structure and function of the protein is necessary to make desired changes by site-directed mutagenesis, a technique already well developed. An impressive example of the rational design of monoterpene synthases was given by Kampranis et al. (2007) who converted a 1,8-cineole synthase from S. fruticosa into a synthase producing sabinene, the precursor of α- and β-thujones with a minimum number of substitutions. They went also a step further and converted this monoterpene synthase into a sesquiterpene synthase by substituting a single amino acid that enlarged the cavity of the active site enough to accommodate the larger precursor of the sesquiterpenes, farnesyl pyrophosphate.
Asymmetric Reduction of C=N Bonds by Imine Reductases and Reductive Aminases
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Matthias Höhne, Philipp Matzel, Martin Gand
In summary, bacterial and fungal reductive aminases and engineered variants with improved and reversed stereoselectivity represent a very promising subclass of IREDs. Their potential for efficient reductive amination has been proven, but for many interesting target amines a high excess of the amine nucleophile has still to be employed. Protein engineering might solve this challenge in the near future.
Role of Engineered Proteins as Therapeutic Formulations
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Khushboo Gulati, Krishna Mohan Poluri
Protein engineering is a rapidly evolving field that has made major strides in the era of designing novel proteins with the desired fold and function. The field has gained momentum as a result of development of recombinant DNA technology, high-throughput screening approaches, and supercomputing techniques (Brannigan and Wilkinson, 2002). Protein engineering approaches have been employed to imbibe several key features such as specificity, stability, solubility, activity, and environmental stability in the proteins. Hence, several diverse varieties of proteins have been designed for their various industrial and biomedical applications. Indeed, this field has also made a remarkable progress in the era of “Protein Therapeutics” (Leader et al., 2008; Caravella and Lugovskoy, 2010; Kimchi-Sarfaty et al., 2013).
An adapted consensus protein design strategy for identifying globally optimal biotherapeutics
Published in mAbs, 2022
Yanyun Liu, Kenny Tsang, Michelle Mays, Gale Hansen, Jeffrey Chiecko, Maureen Crames, Yangjie Wei, Weijie Zhou, Chase Fredrick, James Hu, Dongmei Liu, Douglas Gebhard, Zhong-Fu Huang, Akshita Datar, Anthony Kronkaitis, Kristina Gueneva-Boucheva, Daniel Seeliger, Fei Han, Saurabh Sen, Srinath Kasturirangan, Justin M. Scheer, Andrew E. Nixon, Tadas Panavas, Michael S. Marlow, Sandeep Kumar
While not a requirement, most therapeutic proteins can benefit from at least some degree of protein engineering, either in terms of platform process fit, product consistency and stability, or immunogenic potential. Rational design approaches can be used to improve product consistency and chemical stability by reducing the number of post-translational modification motifs, to improve physicochemical attributes such as thermal stability or aggregation propensity, and to address potential complex ‘biological’ phenomena such as immunogenicity. Biotherapeutic engineering, however, is neither a quick nor a straightforward process with predictable outcomes. Indeed, since comprehensive coverage of amino acid sequence space, even constrained to the complementarity-determining regions (CDRs), is cost and time prohibitive, tradeoffs are usually necessary. Thus, identifying an alternative approach to biotherapeutic engineering that takes advantage of sequence diversity emerging from discovery campaigns has immense potential in identifying optimal candidates with the required affinity, specificity, and superior developability profiles.
Bispecific antibodies for immune cell retargeting against cancer
Published in Expert Opinion on Biological Therapy, 2022
Rebecca P Chen, Kenta Shinoda, Pragya Rampuria, Fang Jin, Tin Bartholomew, Chunxia Zhao, Fan Yang, Javier Chaparro-Riggers
Seminal discoveries in modern immunology have deepened our understanding of how the immune system functions on the molecular level and fueled a great deal of interest in immune cell retargeting using antibody-based therapeutics for cancer treatment. While the initial focus was on professional killer T cells following the approval of the T cell engaging bispecific blinatumomab, other players including γδ T cells, NK cells, macrophages, and even neutrophils are considered attractive targets. The last two decades have witnessed some successes through extensive preclinical and clinical investigations, but challenges remain on both efficacy and safety fronts, especially in the solid tumor space. In this review, we highlighted protein engineering approaches being actively pursued to overcome these obstacles and future directions that might prove broadly applicable in the clinic.
Evaluation of the predictive performance of physiologically based pharmacokinetic models for intramuscular injections of therapeutic proteins
Published in Xenobiotica, 2019
Timothy W. Chow, Matthew R. Wright, Cornelis E. C. A. Hop, Harvey Wong
Therapeutic proteins continue to represent an important class of medicines for many diseases. Advances in medical research and protein-engineering technologies have allowed drug developers and manufacturers to fine-tune and exploit desirable characteristics while maintaining safety and efficacy (Lagassé et al., 2017). Four of the five largest selling pharmaceutical products in 2015 were therapeutic proteins with adalimumab, a monoclonal antibody (mAb), taking the top spot (Philippidis, 2016). Unlike small molecule drugs which are commonly administered orally, therapeutic proteins have not been formulated to allow oral administration due to denaturation in the stomach, proteolytic degradation within the gastrointestinal (GI) tract, and minimal absorption through the GI epithelium (Reilly et al., 1997). Therefore, more invasive routes of administration such as intravenous (IV), subcutaneous (SC) and intramuscular (IM) injections are often used. IM injections of therapeutic proteins are administered at several sites including the arm, gluteal and thigh (Weatherspoon, 2016).