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

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