Solid-state packing dictates the unexpected solubility of aromatic peptides
| Autor: | David A. Hales, Xuewei Dong, Ehud Gazit, Bankala Krishnarjuna, Guanghong Wei, Ayyalusamy Ramamoorthy, Santu Bera, Shannon A. Raab, Yiming Tang, Linda J. W. Shimon, David E. Clemmer, Wei Ji |
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| Rok vydání: | 2021 |
| Předmět: |
crystal packing-solubility relationship
Solid-state Beta sheet General Physics and Astronomy Peptide 02 engineering and technology Tripeptide 010402 general chemistry 01 natural sciences Article NMR spectroscopy General Materials Science Solubility Aromatic peptide mass spectrometry chemistry.chemical_classification Aqueous solution Chemistry Biomolecule aggregation General Engineering General Chemistry Nuclear magnetic resonance spectroscopy 021001 nanoscience & nanotechnology Combinatorial chemistry 0104 chemical sciences General Energy 0210 nano-technology |
| Zdroj: | Cell Reports. Physical Science |
| ISSN: | 2666-3864 |
| DOI: | 10.1016/j.xcrp.2021.100391 |
| Popis: | Summary The understanding and prediction of the solubility of biomolecules, even of the simplest ones, reflect an open question and unmet need. Short aromatic tripeptides are among the most highly aggregative biomolecules. However, in marked contrast, Ala-Phe-Ala (AFA) was surprisingly found to be non-aggregative and could be solubilized at millimolar concentrations. Here, aiming to uncover the underlying molecular basis of its high solubility, we explore in detail the solubility, aggregation propensity, and atomic-level structure of the tripeptide. We demonstrate an unexpectedly high water solubility of AFA reaching 672 mM, two orders of magnitude higher than reported previously. The single crystal structure reveals an anti-parallel β sheet conformation devoid of any aromatic interactions. This study provides clear mechanistic insight into the structural basis of solubility and suggests a simple and feasible tool for its estimation, bearing implications for design of peptide drugs, peptides materials, and advancement of peptide nanotechnology. Graphical abstract Highlights Balance between solubility versus aggregation of aromatic peptides is examined Significant differences in solubility are observed for analogous tripeptides Solid-state packing is found to be underlying molecular basis for high solubility Revealing the importance of biology at the solid state in physiology and pathology The solubility of biomolecules in aqueous solutions is a central issue with regard to their physiological and pathological activities. Bera et al. provide insight into the solid-state packing-solubility relationship of biomolecules. This work may further extend the importance of solid-state biology for basic and applied science. |
| Databáze: | OpenAIRE |
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