A procedure has been developed for synthesizing peptides in an aqueous solution with a reusable solid phase. Specifically designed linker molecule is employed to attach peptides to hydrophilic solid phases, enabling Solid Phase Peptide Synthesis (SPPS) in aqueous solutions. The linker molecule is utilized to connect peptides to an anionic exchange resin during peptide synthesis in an aqueous solution. The general structure of the linker molecule is Fmoc-AA-CH2-Ph-Rx-SO3-, the Fmoc (9-fluorenylmethoxycarbonyl) group serves as a protecting group for amino acids. Amino acids (AA) are linked to the solid phase through a structure of Methoxyphenylcarbonyl group, which is cleavable under strong acidic conditions. The sulfate group is present for forming an ionic bond with the solid resin in an aqueous solution. In this procedure, Fmoc-AA are utilized as building blocks for sequentially adding amino acids in peptide synthesis. Due to Fmoc-AA poor solubility in aqueous solutions, a procedure was developed to enhance the solubility of hydrophobic compounds, with a specific emphasis on dissolving Fmoc-protected Amino Acids (Fmoc-AA) in an aqueous solution. This enhancement facilitates SPPS in aqueous conditions with Fmoc-AA as building blocks. Cationic exchange resin, which is reusable, serves as the solid phase. Our research objective is to shift from the use of organic solvents to an aqueous system while maintaining the existing SPPS practices in organic solvents as closely as possible. This transition involves minimal alterations, maintaining consistency with the organic solvent system, except for the utilization of novel peptide linker molecule to hydrophilic solid resins that are commercially available. This approach is designed to facilitate a more readily acceptable transition for the peptide synthesis industry from using organic solvents to aqueous solution, contributing to greener and more sustainable synthetic methodologies. Show less

Objectives Bacterial resistance to conventional antibiotics is a serious public health problem. Over the past decade, small proteins known as antimicrobial peptides (AMPs), natural compounds produced by all prokaryotic and eukaryotic cells have shown promising results in overcoming the growing problems of antibiotic resistance. There are nowadays several peptides of plant origin and rich in cysteines which have shown very good antimicrobial activities. The research of molecules with bactericidal activity is always current event with increase of multi resistance. The present study was undertaken to investigate the in vitro antibacterial activities of four synthesized peptides obtained in 97% yield by the solid phase synthesis method. Method The synthesis reaction was monitored by combined HPLC and LCMS methods and evaluation of the antibacterial property of these synthetized peptides. The antibacterial test was perform using micro dilution method on many species of bacteria, S. epidermidis ATCC 35984, S. aureus ATCC 25923, S. aureus ATCC 8095, E. faecalis ATCC 29212, E. faecium ATCC 700221, K. pneumoniae ATCC 700603, E. coli ATCC 25922, A. baumannii ATCC 19606, P. aeruginosa ATCC 27853. Results The conformity and effectiveness of the synthesis of the peptides was carried out by LCMS with an average yield of 91%. Peptides were bactericidal on almost all of these strains excepted E. coli ATCC 25922 where it was bacteriostatic. The biofilm eradication capacity test was carried out on two ATCC strains of S. epidermidis. Strain 35984 is a good biofilm-forming strain, while strain 12228 is considered a poor biofilm former. Comparison of the presence of biofilm between them showed a significant difference with p<0.05, showing that the controls used are significantly different in all cases. Conclusion Antimicrobial peptides are a good alternative today to fight against microbial resistance. In view of the results obtained, the different Neo peptides could serve as a basis for preclinical approaches to potential new active ingredients to combat certain microbial resistance. Show less

Amyloid fibrils, which are caused by abnormal conformation and the mis-assembly of proteins, are responsible for several conformational diseases, including prion diseases. To develop methods to prevent amyloid formation, blocking peptides with hydrophilic substitutions covering the stem forming regions of barnase 1-24 were prepared and examined for their ability to block amyloid-forming fragments—prion, Amyloid β, Pmel 17—. When these fragments were mixed with the synthetic blocking peptides, the result was a decline in the intensity of fluorescence, suggesting that amyloid formation was inhibited. Therefore, amyloidogenesis appears to be specifically inhibited by disrupting the hydrophobic interactions between core amyloid regions. Show less

A new approach to protecting the side chain of lysine during solid-phase peptide synthesis in an aqueous environment is explored. The objectives of this study are twofold: 1) to reduce the consumption of chemical solvents in peptide synthesis, and 2) to lower the costs associated with lysine side chain protection. In an effort to minimize the usage of organic solvents in amino acid side chain protection for peptide synthesis,18-crown-6 molecule (18C6) was introduced as protective agent for Lysine (Lys) side chain protection. 18C6 is utilized to protect ε-amino group of on side chain of Lys in peptide synthesis. 18C6 features cavity at its center. The 18C6 molecules exhibit a unique and distinctive host-guest affinity towards ε-amino group on side chain of Lys. 18C6 bind to Lys side chain through hydrogen bonds with ε-amino group of Lys, eliminating the need for chemical reactions in organic solvents to attach protective molecules to the side chain groups. This simplifies the side chain protection procedure significantly for Lys, reducing the consumption of organic solvents. Consequently, this procedure offers advantages for contributing to a greener planet by minimizing chemical reactions and organic solvent usage. Additionally, the cost of side chain protection of Lys is dramatically reduced. Show less