Oligonucleotide-based systems for input-controlled and non-covalently regulated protein binding

Battle, Cooper H.; Chu, Xiaozhu; Jayawickramarajah, Janarthanan

doi:10.1080/10610278.2013.810337

Cited by 10 publications

(10 citation statements)

References 112 publications

(92 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We hypothesized that if one of the protein targets for such synthetic protein binders would be located on the cell surface, their regulatory effect 21 could be extended from the protein level to the cellular level. We also expected that the ability to reversibly change the structure of such DNA-based protein binders [11][12][13][14][15][16][17][18][19][20][21][22] and precisely control the orientation, distance, and valency of their binding units [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] would enable such systems to act as artificial CSPs. Namely, as artificial receptors that respond to dynamic changes in the environment and can endow the bacteria with engineered properties.…”

Section: Resultsmentioning

confidence: 99%

“…The advantages of using ODN-small-molecule conjugates as synthetic protein binders include the ability to precisely control the orientation, distances, and valency of their binding units [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] , as well as the ability to dynamically change their structure, which provides a means to regulate protein functions in real time [11][12][13][14][15][16][17][18][19][20][21] . This work shows that when synthetic protein binders of this class are attached to cell surfaces, their regulatory effect can be extended from the protein level to the cellular level.…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, considerable attention has been devoted to developing protein binders based on oligodeoxynucleotide (ODN)-small-molecule conjugates [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] that, similar to CSPs, can respond to external stimuli and undergo dynamic structural changes that enable them to reversibly interact with proteins and regulate their functions [11][12][13][14][15][16][17][18][19][20][21] . We have recently developed protein binders based on ODN-small-molecule conjugates [21][22][23] and have shown that such binders can be designed to reversibly interact with different proteins 21,22 and even mediate unnatural protein-protein communication processes 21 .…”

mentioning

confidence: 99%

“…Inspired by recent successes in dynamically controlling protein functions and binding interactions with ODN-small-molecule conjugates [11][12][13][14][15][16][17][18][19][20][21] and in cell surface engineering , we set out to develop a dynamic artificial receptor system that combines principles from both research areas. Specifically, we hypothesized that by attaching DNA-based, stimuli-responsive protein binders on the surfaces of living bacteria, at a specific position, and by using solely self-assembly processes, a biomimetic system that imitates the dynamic features of natural CSPs can be obtained.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Decorating bacteria with self-assembled synthetic receptors

et al. 2020

View full text Add to dashboard Cite

The responses of cells to their surroundings are mediated by the binding of cell surface proteins (CSPs) to extracellular signals. Such processes are regulated via dynamic changes in the structure, composition, and expression levels of CSPs. In this study, we demonstrate the possibility of decorating bacteria with artificial, self-assembled receptors that imitate the dynamic features of CSPs. We show that the local concentration of these receptors on the bacterial membrane and their structure can be reversibly controlled using suitable chemical signals, in a way that resembles changes that occur with CSP expression levels or posttranslational modifications (PTMs), respectively. We also show that these modifications can endow the bacteria with programmable properties, akin to the way CSP responses can induce cellular functions. By programming the bacteria to glow, adhere to surfaces, or interact with proteins or mammalian cells, we demonstrate the potential to tailor such biomimetic systems for specific applications.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Decorating bacteria with self-assembled synthetic receptors

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Systems responsive to DNA, RNA, and protein inputs have found application in signal amplification, targeted disease diagnosis, signal thresholding, consensus gating, and feedback control . Hybridization with DNA/RNA has been used to modulate the binding of a phosphopeptide–PNA conjugate to the SH2 domain of Src kinase (Src‐SH2) .…”

Section: In Situ Protein Interferencementioning

confidence: 99%

Nucleic Acid Templated Reactions for Chemical Biology

Pisa

Seitz

2017

ChemMedChem

View full text Add to dashboard Cite

Nucleic acid directed bioorthogonal reactions offer the fascinating opportunity to unveil and redirect a plethora of intracellular mechanisms. Nano‐ to picomolar amounts of specific RNA molecules serve as templates and catalyze the selective formation of molecules that 1) exert biological effects, or 2) provide measurable signals for RNA detection. Turnover of reactants on the template is a valuable asset when concentrations of RNA templates are low. The idea is to use RNA‐templated reactions to fully control the biodistribution of drugs and to push the detection limits of DNA or RNA analytes to extraordinary sensitivities. Herein we review recent and instructive examples of conditional synthesis or release of compounds for in cellulo protein interference and intracellular nucleic acid imaging.

show abstract

Targeted Protein Surface Sensors as a Tool for Analyzing Small Populations of Proteins in Biological Mixtures

et al. 2014

View full text Add to dashboard Cite

Optical cross-reactive sensor arrays (the so-called chemical "noses/tongues") have recently been demonstrated as a powerful tool for high-throughput protein detecting and analysis. Nevertheless, applying this technology to biomarker detection is complicated by the difficulty of non-selective sensors to operate in biological mixtures. Herein we demonstrate a step toward circumventing this limitation by using selfassembled fluorescent receptors consisting of two distinct recognition motifs: specific and non-specific. When combined in an array, binding cooperatively between the specific and non-specific protein binders enables the system to discriminate among closely related isoform biomarkers even in the presence of serum proteins or within human urine.In recent years, extensive efforts have been made to develop non-reductionist approaches to disease diagnosis. Profiling the expression of multiple proteins, rather than detecting individual protein analytes, has been explored as a means of improving diagnostic accuracy and better understanding the parameters affecting disease states.[1] A promising method for obtaining multiplexed protein analysis involves the use of antibodies that can bind and detect the proteins of interest with high affinity and selectivity. [1b,c] This approach has found widespread applications in medical diagnosis; however, the need for producing an antibody for each target and for using stepwise protocols, in addition to their relatively high costs and instability, hamper high-throughput analysis.Cross-reactive sensor arrays, inspired by the mammalian olfactory system, have recently emerged as an alternative detection method that may address these limitations. [2, 3] When the "nose/tongue" approach is used, proteins can be rapidly differentiated using an array of non-specific synthetic receptors that, in combination, generate a unique optical "fingerprint" upon interacting with each protein. Unlike antibody arrays, which operate according to the "lock and key" paradigm, arrays that rely on differential sensing [4] do not require manufacturing multiple antibodies or using technically challenging procedures. As a result, such systems can straightforwardly discriminate among multiple different proteins [3] as well as profile protein mixtures in biofluids, which may indicate disease states. [3f-i] Despite the numerous advantages of cross-reactive arrays, applications for this technology in medical diagnostics are limited by the difficulty of non-selective receptors to operate within biological mixtures. Human serum contains more than 20 000 proteins, of which only about 20 proteins constitute about 99 % of the serum protein mass. Thus, although such systems can effectively discriminate among combinations and concentrations of common serum proteins, [3g] detecting lowabundance disease biomarkers remains challenging. Herein, we present an integrated sensing scheme that uses both the "lock and key" and "differential sensing" strategies for discriminating among low-concentration pr...

show abstract

Oligonucleotide-based systems for input-controlled and non-covalently regulated protein binding

Cited by 10 publications

References 112 publications

Decorating bacteria with self-assembled synthetic receptors

Decorating bacteria with self-assembled synthetic receptors

Nucleic Acid Templated Reactions for Chemical Biology

Targeted Protein Surface Sensors as a Tool for Analyzing Small Populations of Proteins in Biological Mixtures

Contact Info

Product

Resources

About