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Nature uses a variety of tools to mediate the flow of information in cells, many of which control distances between key biomacromolecules. Researchers have thus generated compounds whose activities stem from interactions with two (or more) proteins simultaneously. In this Perspective, we describe how these 'bifunctional' small molecules facilitate the study of an increasingly wide range of complex biological phenomena and enable the drugging of otherwise challenging therapeutic targets and processes. Despite their structural and functional differences, all bifunctional molecules employ Nature's strategy of altering interactomes and inducing proximity to modulate biology. They therefore exhibit a shared set of chemical and biophysical principles that have not yet been appreciated fully. By highlighting these commonalities-and their wide-ranging consequences-we hope to chip away at the artificial barriers that threaten to constrain this interdisciplinary field. Doing so promises to yield remarkable benefits for biological research and therapeutics discovery.
This article was published in the following journal.
Name: Nature chemical biology
Heterobifunctional molecules have proven powerful tools to induce ligase-dependent ubiquitination of tar-get proteins. We describe here a chemical strategy for controlling a different post-translation...
DNA-functionalized gold nanoparticles (AuNPs) often encounter various small molecules and ions such as backfilling agents, bifunctional crosslinkers, stabilizers, and molecules from biological fluids ...
After the first seed concept introduced in the 18th century, different disciplines have attributed different names to dual-functional molecules depending on their application, including bioconjugates,...
The lipase from Pseudomonas fluorescens (PFL) was adsorbed on superparamagnetic NiZnFeO octyl-nanoparticles via interfacial activation, producing the biocatalyst OCTYL-NANO-PFL. In order to further im...
Coordinative alignment of target small molecules onto a chiral metal-organic framework (MOF-520) provides a powerful method to determine the structures of small molecules through single-crystal X-ray ...
The purpose of this study is to evaluate the effect of small molecule therapy in primary cells derived from patients with lysosomal storage disease. The study will focus on activity of sma...
Demethylating agent decitabine enhances the immunogenicity of leukemia cells by inducing the expression of cancer testis antigens (CTAs),MHC class I and II molecules,costimulatory molecule...
The purpose of this study is to test an intervention to introduce and implement proximity alarms on the risk of falls in hospitalized patients.
This is a bioimaging study of 89Zr-M7824 PET scans in patients with advanced or metastatic non-small cell lung cancer who will be receiving M7824 alone or with standard of care chemotherap...
New studies indicate that in about 1 - 2 percent of the younger stroke patients the cause could have been an undiagnosed genetic disease, the so called Fabry disease. In this case certain ...
A mass spectrometric technique that is used for the analysis of large biomolecules. Analyte molecules are embedded in an excess matrix of small organic molecules that show a high resonant absorption at the laser wavelength used. The matrix absorbs the laser energy, thus inducing a soft disintegration of the sample-matrix mixture into free (gas phase) matrix and analyte molecules and molecular ions. In general, only molecular ions of the analyte molecules are produced, and almost no fragmentation occurs. This makes the method well suited for molecular weight determinations and mixture analysis.
A type of FLUORESCENCE SPECTROSCOPY using two FLUORESCENT DYES with overlapping emission and absorption spectra, which is used to indicate proximity of labeled molecules. This technique is useful for studying interactions of molecules and PROTEIN FOLDING.
Small, punctate nuclear structures found in close proximity to COILED BODIES. They are enriched with SMN COMPLEX PROTEINS and may play a role in the processing of SMALL NUCLEAR RIBONUCLEOPROTEINS.
Techniques for determining the proximity of molecules based on ENERGY TRANSFER between bioluminescent chromophores and acceptor fluorophores that have overlapping emission and absorption spectra.
Organelles in which the splicing and excision reactions that remove introns from precursor messenger RNA molecules occur. One component of a spliceosome is five small nuclear RNA molecules (U1, U2, U4, U5, U6) that, working in conjunction with proteins, help to fold pieces of RNA into the right shapes and later splice them into the message.
Biological therapy involves the use of living organisms, substances derived from living organisms, or laboratory-produced versions of such substances to treat disease. Some biological therapies for cancer use vaccines or bacteria to stimulate the body&rs...