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The CARA® Approach

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.

CARA Receptor Environment schematic diagram