De novo proteins constructed from novel amino acid sequences are distinct from proteins that evolved in nature. Construct K (ConK) is a binary-patterned de novo designed protein that rescues Escherichia coli from otherwise toxic concentrations of copper. ConK was recently found to bind the cofactor PLP (pyridoxal phosphate, the active form of vitamin B 6 ). Here, we show that ConK catalyzes the desulfurization of cysteine to H 2 S, which can be used to synthesize CdS nanocrystals in solution. The CdS nanocrystals are approximately 3 nm, as measured by transmission electron microscope, with optical properties similar to those seen in chemically synthesized quantum dots. The CdS nanocrystals synthesized using ConK have slower growth rates and a different growth mechanism than those synthesized using natural biomineralization pathways. The slower growth rate yields CdS nanocrystals with two desirable properties not observed during biomineralization using natural proteins. First, CdS nanocrystals are predominantly of the zinc blende crystal phase; this is in stark contrast to natural biomineralization routes that produce a mixture of zinc blende and wurtzite phase CdS. Second, in contrast to the growth and eventual precipitation observed in natural biomineralization systems, the CdS nanocrystals produced by ConK stabilize at a final size. Future optimization of CdS nanocrystal growth using ConK—or other de novo proteins—may help to overcome the limits on nanocrystal quality typically observed from natural biomineralization by enabling the synthesis of more stable, high-quality quantum dots at room temperature.
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This content will become publicly available on May 9, 2026
Biomineralization of semiconductor quantum dots using DNA-functionalized protein nanoreactors
Proteins can template the heterogeneous nucleation and growth of size-confined nanocrystals. However, protein-templated mineralization often leads to particles that exhibit low colloidal stability, poor crystal quality, and/or diminished photoluminescence. Here, we report protein cage–spherical nucleic acids (SNAs) that can be used as nanoreactors for quantum dot (QD) synthesis and subsequent intracellular delivery. The resulting QD-SNA structures are monodisperse, colloidally stable, and photoluminescent in aqueous solution. The nanoreactors were prepared using two different proteins (~10 and 12 nanometers in diameter), and CdS, CdSe, and PbSe nanocrystals were synthesized. Moreover, the extent of surface defects and crystallinity depends on the relative concentrations of ionic precursors, which control the growth rate and the number of ionic vacancies. By optimizing conditions, CdS-SNAs that exhibit near-zero reabsorption loss were synthesized. Last, QD-SNAs exhibit enhanced cellular uptake and minimal cytotoxicity when compared to commercial QD-protein conjugates, making them potentially useful in bioimaging and diagnostic applications.
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- Award ID(s):
- 2428112
- PAR ID:
- 10631744
- Publisher / Repository:
- AAAS
- Date Published:
- Journal Name:
- Science Advances
- Volume:
- 11
- Issue:
- 19
- ISSN:
- 2375-2548
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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