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Structural Design for Molecular Catalysts
Published in Qingmin Ji, Harald Fuchs, Soft Matters for Catalysts, 2019
Qingmin Ji, Qin Tang, Jonathan P. Hill, Katsuhiko Ariga
TSILs may also act as liquid supports for certain combinatorial synthesis. In peptide synthesis, the molecules are bound to a solid phase throughout the synthesis and only cleaved until the last step. TSILs can be a linker to the liquid phase in the synthesis processes. Miao and Chan used a hydroxy-functionalized imidazolium IL for the synthesis of oligopeptides [200]. NMR studies showed that these chiral ILs exhibit intramolecular as well as intermolecular enantiomeric recognition. Good yield of a pentapeptide without the need for chromatography can be achieved. Same approach was also utilized for multi-step synthesis of drugs [201, 202]. Compared with other supports, these liquid supports may have higher loading capacity, facial analysis on the intermediates.
Synthesis of Bioactive Peptides for Pharmaceutical Applications
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Jaison Jeevanandam, Ashish Kumar Solanki, Shailza Sharma, Prabir Kumar Kulabhusan, Sapna Pahil, Michael K. Danquah
Basic principle: Chemical synthesis of peptides involves the mechanism of protection and activation. The activation of the carboxylic acid (RCOOH) by chemical reagents in the amino acid generates active acyl group (R-CO-) that forms strong peptide bonds, followed by nucleophilic α-amino group attack (H2N-R). The protection of the sensitive functional clusters that are not included in the formation of peptide bond (Machado et al., 2004) are envisioned to enhance chemical selectivity that are essential for the precise sequence of peptide synthesis (David and Luis, 2001). There are three methods of chemical-based peptide synthesis and they are solution, solid phase, and sequential fragment condensation.
Evaluation of greener solvents for solid-phase peptide synthesis
Published in Green Chemistry Letters and Reviews, 2021
Katarzyna Wegner, Danielle Barnes, Kim Manzor, Agnieszka Jardine, Declan Moran
First reported by R.B. Merrifield in early 1963, solid-phase peptide synthesis (SPPS) is the most commonly used method for the production of peptides in both research laboratories and in the pharmaceutical industry today (1). SPPS involves the use of a solid-phase support, typically a resin, which acts as an anchor for the addition of the first Nα protected C-terminal amino acid that is coupled to the solid support, followed by the removal of the Nα protecting group. This process is repeated until the desired peptide sequence is synthesized (Figure 1) (2–5).
New approaches towards the discovery and evaluation of bioactive peptides from natural resources
Published in Critical Reviews in Environmental Science and Technology, 2020
Nam Joo Kang, Hyeon-Su Jin, Sung-Eun Lee, Hyun Jung Kim, Hong Koh, Dong-Woo Lee
Traditionally, peptide synthesis has been segmented into solid-phase synthesis, liquid-phase synthesis, and hybrid synthesis. These approaches have a number of advantages, such as ease of operation, easy purification, short production cycles, high-level automation, and the ability to synthesize long peptides using small quantities of amino acids (Fields, 2002). We will not discuss chemical synthesis approaches in detail here due to the availability of several excellent reviews on this topic (Bray, 2003; Palomo, 2014). Among biological alternatives of peptide synthesis, microbial fermentation and enzymatic hydrolysis are the most efficient in terms of increasing oral bioavailability, decreasing adverse effects, ensuring drug safety and efficacy, imparting protease resistance, and developing formulations (Pandey, Naik, & Vakil, 2015). Nevertheless, their components or the biological process for natural BP production has several concerns about immunogenicity or biological impurities including viruses (Cantani & Micera, 2000, 2001). Biological routes to the production of BPs derived from natural resources, referred to as natural BPs, are in great demand; these compounds will be used to combat diseases with major impacts on the functions or health of organisms, especially humans and animals. In general, these peptides are inactive within the sequence of the parent protein molecule (referred to as the propeptide) and can be liberated by gastrointestinal in vivo digestion of proteins, bacterial fermentation of natural resources, or hydrolysis by proteolytic enzymes. Several systematic approaches to standardizing the cultivation of microorganisms on food-derived plant and animal sources will increasingly require the application of modern techniques in genomics, molecular biology, biochemistry, and analytical and information sciences.
A secretory system for extracellular production of spider neurotoxin huwentoxin-I in Escherichia coli
Published in Preparative Biochemistry & Biotechnology, 2022
Changjun Liu, Qing Yan, Ke Yi, Tianhao Hu, Jianjie Wang, Zheyang Zhang, Huimin Li, Yutao Luo, Dongyi Zhang, Er Meng
The conventional approach for identifying individual cysteine-rich peptides from complex venoms usually demanded various purification methods, such as gel filtration, reversed-phase high performance liquid chromatography (RP-HPLC), and ion-exchange chromatography.[10,11] In general, according to the traditional methods, extensive cysteine-rich peptides in high abundance might be identified and analyzed preferentially. Additionally, large amounts of studies demonstrated that not only the high-abundance cysteine-rich peptides but also the low-abundance ones may need to be analyzed. However, it was difficult to isolate the low-abundantly bioactive peptides due in large part to the incredible complexity of crude venoms, the lack of appropriate technologies to extract components with tiny amounts, and the requirements for expensive equipment and highly skilled researchers.[3,11,12] Moreover, by genomic, proteomic and transcriptomic analysis of venom glands, the number of putative coding sequences of diversified toxins of animal venoms has shown an explosive growth trend in recent decades.[13–15] The solid-phase peptide synthesis method has been used to synthesize amounts of peptides, especially when containing non-native and modified amino acid residues.[16] Although several methods have been invented to achieve the correct formation of cysteine-rich peptides,[17–19] the solid-phase peptide synthesis method was not considered to be the optimal strategy for producing cysteine-rich peptides because of its high cost. Due to the advantages of easy genetic manipulation, rapid cell growth, high efficiency, and low cost, heterologous expression in Escherichia coli has been proven to be an efficient and economical alternative to synthesize peptides or proteins.[11,20] However, when overexpressed in cytoplasmic space, it is challenging to obtain heterologous cysteine-rich peptides or proteins in soluble form, due to the adverse reducing environment in cytoplasm for correct folding of disulfide bonds produced by the thioredoxin system and/or the glutaredoxin/glutathione system.[21,22] In order to overcome the problems, two engineered E. coli strains, the strains OrigamiTM and its derivatives, in which the two encoding genes of both glutathione reductase (gor) and thioredoxin reductase (trxB) were mutated, and the strain SHuffleTM, in which the encoding gene of cytoplasmic disulfide isomerase protein (DsbC) was introduced except for the trxB and gor double mutation, could be used as heterologous expression hosts for the disulfide bond formation.[23,24]. Additionally, an alternative approach would be selected to introduce them into relatively oxidizing periplasm of E. coli, where correct disulfide bonds folding of endogenous cysteine-rich peptides/proteins takes place by both DsbA/DsbB pathway that guides the folding of disulfide bridges and DsbC/DsbD pathway that introduces the isomerization of disulfide bridges.[25–27] A series of signal peptides, such as MalE, PelB, and DsbC, have been used to successfully direct the cysteine-rich peptides or proteins to periplasm of E. coli.[28–30]