A novel method developed by researchers allows for the precise creation of four-stranded β-sheets using metal-peptide coordination, as reported by scientists at the Institute of Science Tokyo. This cutting-edge technique solves persistent issues related to the controlled formation of β-sheets, such as fibril aggregation and unwanted isomer variations in the end product. Such advancements could significantly enhance the exploration and utilization of β-sheets in the fields of biotechnology and nanotechnology.
A novel method developed by researchers enables the precise construction of four-stranded β-sheets through metal-peptide coordination, as reported by experts from the Institute of Science Tokyo. This innovative technique tackles persistent issues related to controlled β-sheet formation, such as fibril aggregation and erratic isomer variations in the final product. This advancement could significantly further studies and applications of β-sheets in biotechnology and nanotechnology.
Besides the natural sequence of amino acids that construct a protein, the three-dimensional organization is crucial to its function. For instance, β-sheets, which are flat structures formed through hydrogen bonds between adjacent peptide strands, are vital for protein stability and folding. They are also linked to several neurodegenerative diseases, including Alzheimer’s. On the other hand, engineering β-sheets offers potential benefits in biotechnology, medicine, and nanomaterials science.
However, creating β-sheet assemblies with a specific number of strands poses significant challenges for two main reasons. First, multi-stranded β-sheets often clump together into aggregates called fibrils, which can easily become insoluble, altering or eliminating their biological functions. Second, when peptide strands are assembled during β-sheet production, numerous structural isomers can form. As a result, the produced assemblies frequently exhibit unpredictable strand orientations, alignments, or quantities, complicating the creation of a target compound. Therefore, a novel method for generating tailored β-sheets is essential.
In a recent study published in Angewandte Chemie International Edition on October 22, 2024, a research team led by Associate Professor Tomohisa Sawada from the Institute of Science Tokyo (Science Tokyo), Japan, aimed to address these challenges. Their findings demonstrated a promising method for producing four-stranded β-sheets using silver atoms as coordination centers in metal-peptide interactions.
The researchers engineered a pentapeptide known as ‘1,’ where the second and fourth amino acid residues were modified with 3-pyridyl-substituted alanine. These pyridyl groups were placed on opposite sides of the main chain and served as sites for interacting with silver atoms. When silver (Ag) was introduced, two ‘1‘ molecules would bond together to create an Ag2(1)2 ring as a proposed intermediate. Notably, due to the reversible nature of metal coordination during the reaction, pairs of Ag2(1)2 rings became interlocked, with hydrogen bonds between neighboring pentapeptides maintaining the overall structure of the β-sheet.
The researchers confirmed the successful creation of these interlocked structures, [Ag2(1)2]2, through nuclear magnetic resonance and X-ray crystallography studies. Impressively, the resulting four-stranded β-sheets formed a singular type of isomeric structure without aggregation. In simpler terms, all β-strands were composed of two interlocked rings, with the first and third strands oriented in one direction, while the second and fourth strands faced the opposite way. Additionally, the positioning of the interlocking metal-complexation sites was consistent across all β-strands produced. “Our findings revealed that the combination of β-sheet amide hydrogen bond formation and metal cross-linking of side chains minimizes the number of possible isomers. In essence, we demonstrated that non-covalent side chain cross-linking can induce highly selective single-structure β-sheets in a defined format,” noted Sawada.
The insights gained from this research could facilitate the exploration of β-sheets, unlocking their potential for next-generation biotechnology and nanotechnology. “To our knowledge, this is the first instance of constructing a precise four-stranded β-sheet assembled purely from non-covalent interactions. We believe our approach paves the way for rational construction of β-sheet structures and their functions in the future,” concluded Sawada, expressing enthusiasm about the future possibilities.
