A Multivalent Structure‐Specific RNA Binder with Extremely Stable Target Binding but Reduced Interaction with Nonspecific RNAs

Abstract

By greatly enhancing binding affinities against target biomolecules,m ultivalent interactions provide an attractive strategy for biosensing.However,there is also amajor concern for increased binding to nonspecific targets by multivalent binding.Ar ange of charge-engineered probes of as tructurespecific RNAbinding protein PAZaswell as multivalent forms of these PAZp robes were constructed by using diverse multivalent avidin proteins (2-mer,4 -mer,a nd 24-mer). Increased valency vastly enhanced the binding stability of PAZtostructured target RNA. Surprisingly,nonspecific RNA binding of multivalent PAZcan be reduced even belowthat of the PAZm onomer by controlling negative charges on both PAZand multivalent avidin scaffolds.The optimized24-meric PAZs howed nearly irreversible binding to target RNAw ith negligible binding to nonspecific RNA, and this ultra-specific 24-meric PAZp robe allowed SERS detection of intact micro-RNAs at an attomolar level.

Multivalent Antibody–Nanoparticle Conjugates To Enhance the Sensitivity of Surface-Enhanced Raman Scattering-Based Immunoassays

“…Immunoassays are one of the most commonly used rapid and sensitive analytical methods for the detection and quantification of biomolecules in a wide range of fields, including disease diagnosis, food safety, and environmental monitoring . Recent immunoassays have employed various types of readout signals, including color change, surface plasmon resonance (SPR), fluorescence, electrochemistry, and surface-enhanced Raman scattering (SERS), advancing into sophisticated analyte detection methods. Among various types of immunoassays, SERS-based immunoassays have attracted much attention because of their single-molecule sensitivity, photostability, and excellent multidetection capability .…”

Multivalent Traptavidin–DNA Conjugates for the Programmable Assembly of Nanostructures

“…26−28 Hence, they have been used in various applications of protein-based supramolecular structures such as smart nanocarriers, 29,30 biological nanoenzymes, 31,32 and nanobiosensors. 33 While DNA and protein have proven themselves immensely useful in nanoscience and nanotechnologies, they may work together synergistically to extend their utilities by adjoining unlimited design flexibility of DNA and extreme structural and functional diversities of protein. Although the site-specific binding of protein−DNA conjugation is still challenging, several chemical conjugation methods have been recently developed to precisely coordinate the molecular components at nanoscale.…”