The+one-bead+one-compound+combinatorial+library+method

The One-Bead-One-Compound combinatorial library method

The One-Bead-One-Compound (OBOC) combinatorial libraries are based on the "split synthesis" approach. In "split synthesis" approach, resin beads are split and coupled with monomers A 1 to A 3 (for the example in figure 1). After this step, the resins are mixed, washed, deprotected, and then are split again [2 ]. The resins are now coupled with monomers B 1 to B 3  [2 ]. After this the resins are mixed, washed, deprotected, and split again. Resins are now reacted with monomers C 1 to C 3 and then mixed together. This process is repeated until the end of solid phase synthesis [2 ].

Figure 1 : A diagrammatic representation of the "split synthesis approach". The details of each step are described in the text above. The main advantage of using split synthesis approach, when generating combinatorial library, is that each resin bead on which the library is synthesized binds only a single compound, even though a single 100um diameter bead may contain 10 13 copies of this single compound [1]. As a result, this approach was named the one-bead-one-compound combinatorial library method. After the generation of the library, a target molecule is used to screen the library and, as with all combinatorial library types, the beads expressing the compound (e.g. peptide or other oligomer) that interacts most favourably will bind the target molecule [1]. This interaction between the suitable compound present on the bead and the target can be identified as a “positive” bead through direct or indirect detection methods, such as colour change or fluorescent probes, respectively [1].

The OBOC method was first successfully used to identify peptide ligands for the ant-β-endorphin monoclonal antibody, but has since been used extensively as an interrogative method by researchers in a variety of fields. OBOC libraries can remain on the solid support or can be removed and placed into a segregated liquid phase through the cleavage of orthogonal linkers that connect the compounds to the solid suppor t [1].

One of the biggest advantages of OBOC method is that a large library of compounds can be generated using this method [1]. Further, OBOC libraries are inexpensive and easy to make [1]. The libraries generated can include non-biological monomers and D-amino acids, because of the non-biological nature of their synthesis [1]. As mentioned above, the libraries can either remain on the solid support or be cleaved into a segregated liquid phase. The screening of OBOC libraries is highly efficient, making the screening of a 10 7 member library a one-day-one-person task [1].

As with all combinatorial library types, OBOC does have limitations. The two major limitations identified for OBOC libraries are that the linker that connects the library member to the solid support can affect the chemistry of the library member, and that the structure of the library member needs to be elucidated after the positive bead has been identified [1].

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