Topics

Unifying principles of bifunctional, proximity-inducing small molecules.

08:00 EDT 1st April 2020 | BioPortfolio

Summary of "Unifying principles of bifunctional, proximity-inducing small molecules."

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.

Affiliation

Journal Details

This article was published in the following journal.

Name: Nature chemical biology
ISSN: 1552-4469
Pages: 369-378

Links

DeepDyve research library

PubMed Articles [11037 Associated PubMed Articles listed on BioPortfolio]

Heterobifunctional molecules induce dephosphorylation of kinases - a proof of concept study.

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...

Effects of Small Molecules on DNA Adsorption by Gold Nanoparticles and a Case Study of Tris(2-carboxyethyl)phosphine (TCEP).

DNA-functionalized gold nanoparticles (AuNPs) often encounter various small molecules and ions such as backfilling agents, bifunctional crosslinkers, stabilizers, and molecules from biological fluids ...

Designing Chimeric Molecules for Drug Discovery by Leveraging Chemical Biology.

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,...

Further stabilization of lipase from Pseudomonas fluorescens immobilized on octyl coated nanoparticles via chemical modification with bifunctional agents.

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 in the Pores of MOFs for the Structural Determination of N-, S-, and P-Containing Organic Compounds Including Complex Chiral Molecules.

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 ...

Clinical Trials [4798 Associated Clinical Trials listed on BioPortfolio]

Cellular Pharmacodynamics of Small Molecules in Lysosomal Storage Disorders

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...

Decitabine Based Chemotherapy Followed by Haploidentical Lymphocyte Infusion for Elderly Patients With AML

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...

Proximity Alarms to Reduce Patient Falls

The purpose of this study is to test an intervention to introduce and implement proximity alarms on the risk of falls in hospitalized patients.

Bioimaging Study of 89Zr-M7824 in NSCLC

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...

Stroke in Young Fabry Patients (sifap2): Characterization of the Stroke Rehabilitation

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 ...

Medical and Biotech [MESH] Definitions

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.

Quick Search


DeepDyve research library

Relevant Topic

Biological Therapy
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...


Searches Linking to this Article