Amino Acid Pairing for De Novo Design of Self-Assembling Peptides and Their Drug Delivery Potential

Molecular self‐assembly has emerged as the “bottom‐up” engineering route to fabricate functional supramolecules for diverse applications. The design of molecular building units becomes critical in determining the structure, properties, and function of the resulting assemblies. Here, a de novo design...

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Bibliographic Details
Published in:Advanced functional materials 2011-07, Vol.21 (13), p.2456-2464
Main Authors: Fung, Shan-Yu, Yang, Hong, Sadatmousavi, Parisa, Sheng, Yuebiao, Mamo, Tewodros, Nazarian, Reyhaneh, Chen, P.
Format: Article
Language:English
Subjects:
amino acid pairing
drug delivery
molecular self-assembly
nanostructures
peptides
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Summary:Molecular self‐assembly has emerged as the “bottom‐up” engineering route to fabricate functional supramolecules for diverse applications. The design of molecular building units becomes critical in determining the structure, properties, and function of the resulting assemblies. Here, a de novo design principle of amino acid pairing (AAP) to generate new classes of self‐assembling peptides (SAPs) is presented. In this study, the AAP focuses on hydrogen bonding, and ionic and hydrophobic interactions among amino acid pairs. With solely hydrogen bond pairs, SAPs can be constructed with only two amino acids. With all three AAP strategies (hydrogen bonds, ionic and hydrophobic pairs), a short novel SAP is constructed. This peptide can self‐assemble into β‐sheet‐rich nanofibers with a relatively low “critical aggregation concentration (CAC)” of ∼10 μM. It also shows the ability to stabilize and deliver the hydrophobic anticancer agent ellipticine in aqueous solution. The peptide‐drug complexes/co‐assemblies exhibit anticancer activity against human lung carcinoma cells A549 and breast cancer cells MCF‐7, and have good dilution stability. The presented AAP design provides a new strategy to fabricate functional supramolecules with potential applications in nanomedicine. A de novo design principle of amino acid pairing (AAP) to generate new classes of self‐assembling peptides is proposed. The AAP assembly utilizes hydrogen bonding, and ionic and hydrophobic interactions among amino acid pairs to form stable nanostructures. Using these three strategies, a short novel self‐assembling peptide is constructed. It can form stable nanofibers and shows a potential in stabilizing and delivering the hydrophobic anticancer model drug ellipticine in aqueous solution.
ISSN:1616-301X
1616-3028
1616-3028
DOI:10.1002/adfm.201002497