1. Preparation, Characterization and Pharmacokinetic Study of N-Terminal PEGylated D-Form Antimicrobial Peptide OM19r-8
Qi Cui, Qi-Jun Xu, Lei Liu, Li-Li Guan, Xiu-Yun Jiang, Muhammad Inam, Ling-Cong Kong, Hong-Xia Ma J Pharm Sci. 2021 Mar;110(3):1111-1119. doi: 10.1016/j.xphs.2020.10.048. Epub 2020 Oct 28.
Recently, new cationic antibacterial peptide OM19R has been designed with low minimum inhibitory concentration (MIC) values against some gram-negative bacteria, such as Escherichia coli, Salmonella, and Shigella. However, this hybrid peptide, like most antibacterial peptides, has low enzyme stability and short half-life, which, in turn, increases the drug's cost. In this study, an antibacterial peptide (OM19r-8) was obtained containing some D-Arg amino acids. The new preparations were carried out through the replacement of l-Arginine by d-Arginine and the addition of PEG chains. Firstly, eight OM19r series of antibacterial peptides were obtained by designing D-Arg. Then, a polyethylene glycol-modified product mPEG5-butyrALD-OM19r-8 (mPEG5-OM19r-8) was isolated and purified by reverse-phase high-performance liquid chromatography (RT-HPLC). The enzyme stability test showed that the resistance of antibacterial peptide OM19r-8 to protease degradation increased by 4-32-fold. Moreover, the Time-kill studies showed that the germicidal kinetics curves of mPEG5-OM19r-8 and OM19r-8 to Escherichia coli had a similar trend, thus suggesting that PEG modification has an acceptable effect on the activity of the original peptide. Furthermore, the elimination of half-life (28.09 ± 2.81min) of mPEG5-OM19r-8, and the area under the drug concentration-time curve (2686.48 ± 651.36min*ug/ml) was significantly prolonged. The current study demonstrates an example that optimizes the AMP by utilizing L-to-D amino acid replacement and including PEG chains. These results provide useful data for the clinical application of the mPEG5-OM19r-8.
2. Making Solid-Phase Peptide Synthesis Greener: A Review of the Literature
Kyriakos G Varnava, Vijayalekshmi Sarojini Chem Asian J. 2019 Apr 15;14(8):1088-1097. doi: 10.1002/asia.201801807. Epub 2019 Feb 20.
To date, the synthesis of peptides is concurrent with the production of enormous amounts of toxic waste. DMF, CH2 Cl2 , and NMP are three of the most toxic organic solvents used in chemical synthesis and are the most common solvents used for peptide synthesis. Additionally, concerns about the hepatotoxicity caused by exposure to DMF and from the toxic and allergenic nature of additives used in peptide synthesis necessitates the need for a green, environmentally friendly, and safer protocol for peptide synthesis. This review summarizes the current literature on green solid-phase peptide synthesis successes and challenges encountered. The review concludes with suggestions for future research towards a simple and efficient green peptide synthesis protocol.
3. A Selective Cucurbit[8]uril-Peptide Beacon Ensemble for the Ratiometric Fluorescence Detection of Peptides
Debabrata Maity, Khaleel I Assaf, Wilhelm Sicking, Christoph Hirschhäuser, Werner M Nau, Carsten Schmuck Chemistry. 2019 Oct 11;25(57):13088-13093. doi: 10.1002/chem.201901037. Epub 2019 Sep 17.
A convenient supramolecular strategy for constructing a ratiometric fluorescent chemosensing ensemble, consisting of a macrocyclic host (cucurbit[8]uril CB[8]), and a pyrene-tagged amphiphilic peptide beacon (AP 1), is reported. AP 1 unfolds upon encapsulation of the pyrene termini into the hydrophobic CB[8] cavity. This changes pyrene excimer to monomer emission. Substrates with higher affinity for the CB[8] cavity can displace AP 1 from the ensemble. The released AP 1 folds again to form a pyrene excimer, which allows for the ratiometric fluorescence monitoring of the substrate. In this report, the ensemble capacity for ratiometric fluorescence monitoring of biological substrates, such as amino acid derivatives, specific peptides, and proteins, in aqueous media is demonstrated.
