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RECEPTORS' Combinatorial Artificial Receptor Array (CARA™) technology is designed to be adaptable to a broad spectrum of applications and is the foundation for each of the product platforms. It constitutes a unique approach to the creation of efficient and economical solutions to the challenge of engineered molecular recognition. The performance of our CARA™ products highlights the strengths of this technology: sensitivity, specificity, stability, and scalability.
Molecular recognition is an essential part of many biochemical processes. Fundamentally, recognition is driven by the complementary interaction of two binding partners' respective functionalized surfaces. Unfortunately, the ability to develop targeted binding partners to interesting biomolecules is hindered by our limited understanding of the factors that give rise to molecular recognition. Consequently, the ultimate goal of designing a system for the efficient and effective creation of artificial binding partners to any target remains elusive. To this end, RECEPTORS has developed the Combinatorial Artificial Receptor Array (CARA™ ).
The CARA™ approach is based on the idea of using a small library of subunits to access both the breadth and depth of "binding space". In nature, this strategy is mirrored by antibody-biomolecule binding, which relies on a small repertoire of the twenty common amino acids to achieve a virtually infinite diversity of binding interactions. The key to this success is the combinatorial display of these 20 amino acid "building blocks" within a defined binding pocket. With CARA™, this concept has been combined with the practical notion that receptor environment candidates should be compatible with high-throughput screening methods, where each candidate yields a binding result. Thus, the development of CARA™ was guided by the need to provide both binding space diversity and polyvalent spatial display of a simple set of building blocks in an operationally simple, economic, and flexible format.
The CARA™ system begins with the creation of a limited set of small molecular building blocks. An array of receptor environments is created through the simple solution combination of these building blocks, which are then covalently immobilized to a support surface. This approach takes advantage of the fact that immobilization on the support will reproducibly display all of the regio-, stereo-, and spatial relationships possible for each combination of building blocks, without the need for discrete synthesis. This display, while heterogeneous on a molecular scale, is statistically reproducible on the macro-scale (e.g. a 100 µm microarray spot), yielding a reproducible binding response to a particular target. Kinetic and thermodynamic binding equilibria efficiently select for the highest affinity isomers.
An efficient, economic, and effective affinity reagent development platform must produce receptors which are SENSITIVE, SPECIFIC, STABLE, and SCALABLE. The CARA™ system is a reproducible high-throughput, platform for the identification of sensitive, specific, and stable affinity reagents.
In a typical sample, proteins and other biomolecules will exist at concentrations that span orders of magnitude. For this reason, it is desirable to create receptor arrays that are sensitive enough to detect proteins across wide concentration ranges.
CARA™ receptor arrays have been shown to produce a consistent binding "fingerprint" across a wide range of protein concentrations spanning from less than 1ng/ml to greater than 1µg/ml. These arrays have further been shown to have detection limits of less than 0.1ng/ml
In order for an affinity binding system to be useful, it must not only detect a target molecule, but must also produce differentiable responses to a range of target molecules.
Even a low-density CARA™ array can give reproducible, distinct, and identifiable binding affinity patterns for any number of proteins. The data from these binding patterns are then used to design optimal receptor environments for applications ranging from biomolecule purification supports to microbe detection systems.
Stabilty, both in terms of shelf-life and the ability to retain functionality when faced with harsh environments is another critical factor in the performance and utility of an affinity binding platform.
Our CARA™-derived Receptor Environments are both durable and resilient, compared to many other affinity binding systems currently available. Not only can they can be stored at room temperature for a minimum of 6 months, but their performance is unaffected by exposure to wide range of conditions including common organic solvents (dichloromethane, acetone, ethyl acetate, tetrahydrofuran, isopropanol, aq. ethanol, dimethylformamide, pyridine), acids (pH 4), bases (pH 10), and salts (concentration greater than 1M).
Related Documents:
RECEPTORS LLC Affinity by Design Overview (PDF)