Journal article
Solid-state packing dictates the unexpected solubility of aromatic peptides
Cell Reports. Physical Science, Vol.2(4)
Abstract
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.
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.
Details
- Title
- Solid-state packing dictates the unexpected solubility of aromatic peptides
- Creators
- Santu Bera - Tel Aviv UniversityXuewei Dong - Fudan UniversityBankala Krishnarjuna - University of Michigan–Ann ArborShannon A Raab - Indiana UniversityDavid A Hales - Indiana UniversityWei Ji - Tel Aviv UniversityYiming Tang - Fudan UniversityLinda J.W Shimon - The Weizmann Institute of ScienceAyyalusamy Ramamoorthy - University of Michigan–Ann ArborDavid E Clemmer - Indiana UniversityGuanghong Wei - Fudan UniversityEhud Gazit - Tel Aviv University
- Resource Type
- Journal article
- Publication Details
- Cell Reports. Physical Science, Vol.2(4)
- Publisher
- Cell Press
- Language
- English
- DOI
- https://doi.org/10.1016/j.xcrp.2021.100391
- Record Identifier
- 993269918903596
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