biostudies-literatureSaji MRutgers UniversityFaculty Early Career Development AwardNational Science Foundatione202507844https://www.ebi.ac.uk/biostudies/studies/S-EPMC12363646biostudies-literatureUnknown64(34)Hydrophobic interactions are one of the fundamental driving forces of self-assembly in living systems. It remains challenging to harness hydrophobicity to have a controllable and programmable assembly of DNA nanostructures. On the other hand, there is also a need to explore orthogonal hierarchical assembly strategies to be used as an additional toolset along with the traditional Watson-Crick base pairing to achieve complex superstructures. In this work, we rationally design and synthesize a series of low molecular weight hydrophobic molecules that are conjugated to single-stranded DNA strands. By incorporating these modified DNA strands into the precisely defined locations of DNA tiles and origami nanostructures, we achieve controlled hierarchical assembly driven by hydrophobic interactionAngewandte Chemie (International ed. in English)Controlling Assembly of Hybrid DNA Nanostructures into Higher-Order Structures via Hydrophobicity.PMC12363646DMR-2046835Saji MPerumal DZhang FYang QJaekle FfalseControlling Assembly of Hybrid DNA Nanostructures into Higher-Order Structures via Hydrophobicity.Hydrophobic interactions are one of the fundamental driving forces of self-assembly in living systems. It remains challenging to harness hydrophobicity to have a controllable and programmable assembly of DNA nanostructures. On the other hand, there is also a need to explore orthogonal hierarchical assembly strategies to be used as an additional toolset along with the traditional Watson-Crick base pairing to achieve complex superstructures. In this work, we rationally design and synthesize a series of low molecular weight hydrophobic molecules that are conjugated to single-stranded DNA strands. By incorporating these modified DNA strands into the precisely defined locations of DNA tiles and origami nanostructures, we achieve controlled hierarchical assembly driven by hydrophobic interaction2025-01-01T00:00:00Z2025 Aug2026-04-13T17:10:42.495Z2026-04-07T13:34:20.709ZS-EPMC123636464055279510.1002/anie.202507844