Self-avoiding molecular recognition systems (SAMRS) prevent the binding or interaction of similar molecular analogs with each other.
Because of the enormous diversity of pathogens, pathogen detection methods are needed to identify multiple genetic targets simultaneously. Recent research in synthetic biology produced a variety of non-standard nucleic acid analogs thought to circumvent obstacles encountered when scaling up multiplexed PCR amplification to larger reaction sets.
In 2005, Benner & Sismour reported examples of alternative nucleobases as parts of DNA nucleobases that can be used as interchangeable building modules. The Benner group developed these alternative nucleobases further into AEGIS and SAMRS analogs.
In 2008 and 2010 Hoshika et al. introduced the “Self-Avoiding Molecular Recognition Systems” or SAMRS, which uses DNA analogs that can bind to natural DNA but not other SAMRS analogs. The SAMRS concept utilizes the DNA analogs 2-aminopurine-2'-deoxyriboside (A*), 2'-deoxy-2-thiothymidine (T*), 2'-deoxyinosine (G*), and N4-ethyl-2'-deoxycytidine. These SAMRS DNA analogs bind to their natural DNA targets but not to other SAMRS analogs. SAMRS is very useful for multiplexed polymerase chain reactions.
The SAMRS concept can be applied in supramolecular chemistry, drug delivery, and materials science.
Key Features of SAMRS are:
Selective Binding: SAMRS typically have a specific target molecule they recognize and bind to while avoiding others with similar structural features.
Self-Assembly: Also, SAMRS can self-assemble into larger structures, like nanomaterials or functional materials, without forming undesired aggregates.
Chemical Design: The molecular architecture of SAMRS is not a result of chance. It is carefully designed, using steric hindrance or specific functional groups that favor interactions with the target while minimizing interactions with similar molecules.
Applications: SAMRS has potential uses in sensors, catalysis, drug design, and targeted delivery systems, where selective interaction is crucial for functionality and effectiveness.
Dynamic Behavior: SAMRS are not static entities. They can adapt their interactions in response to environmental changes, enhancing their specificity and efficiency.
Self-avoiding molecular recognition systems are a fascinating area of research combining principles from chemistry, biology, and materials science to create functional and selective molecular interactions.
Chemical Structures of Standard Watson Crick Pairs
Three (3) hydrogen bonds. Two hydrogen bonds.
The SAMRS Concept
SAMRS bases, indicated with a *, can base pair with standard bases in the target but not with other SAMRS bases. The non-standard nucleic acids from the Self-Avoiding Molecular Recognition Systems (SAMRS: A*, T*, G*, and C*) are structurally modified versions of the standard DNA nucleobases (A, T, G, and C) (Hoshika 2008). SAMRS nucleobases maintain the ability to base pair with standard DNA nucleobases but not with their SAMRS complement. Primers modified with SAMRS components anneal to and amplify natural DNA and RNA.
However, SAMRS:SAMRS pairs (T*:A* and C*:G*) are thermodynamically disfavored.
Sharma et al. (2014) showed that most of the undesired side products of recombinase polymerase amplification (RPA) can be avoided if primers contain components of SAMRS suggesting that SAMRS‐RPA may become a powerful tool within the range of amplification techniques available to scientists. RPA is used at low temperatures and does not force the detection system to recreate base‐pairs following Watson–Crick rules, hence it produces undesired products that can impede the amplification of desired products, complicating analysis.
Wang et al. (2020) showed that the use of water-soluble graphene oxide and SAMRS primers significantly improved the specificity of recombinase polymerase amplification (RPA) detection.
Yang et al. (2020) utilized SAMRS nucleobases for the elimination of primer dimers for improved SNP detection.
Babar et al. (2024) used computational methods for the study of modified DNA nucleobase sensing on monolayers of MoS2 and MoSSe. The results of this study indicated that MoSSe (Se side) monolayers are a promising platform for the selective detection of DNA bases.
Kawabe et al. (2024) utilized SAMRS together with the artificially expanded genetic information system (AEGIS) and next-generation sequencing for amplicon identification to avoid primer dimer formation in specific multiplexed PCR assays. Using this approach, Kawabe et al. showed that a low-cost, portable sequencing platform allows high throughput analysis of wastewater, soil, and human stool samples.
Reference
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SAMRS [Firebirdbio]
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Patent EP2321332A1: Granted 2017-03-27, active, anticipated expiration 209-08-19. [EP2321332A1]
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