ABSTRACT In an affinity precipitation, a substance is almost exclusively transferred and thus separated from solution into a newly formed solid phase because it is capable of participating in a specific biochemical interaction. From the viewpoint of the growing biopharmaceutical industry the method is highly promising, since it combines the selectivity of an affinity separation with the robustness and the scalability of a conventional precipitation. One way to bring about an affinity precipitation is the formation of large and finally insoluble complexes between a multivalent affinity ligand and the (at least bivalent) target molecule. In this case the precipitate formation is the direct result of the affinity interaction itself. A much more general approach, which can also be used for monovalent target molecules, is to use so-called affinity macroligands, i.e. reversibly water-soluble polymers that carry a specific product-binding domain. While the former type of affinity precipitation is very much defined by the biological parameters of a given system, the latter depends for its success on the availability of well-designed “intelligent” macromolecules. These molecules need to be compatible to and functional in complex feeds such as cell culture supernatants, cell lysates and homogenates as well as the tissue and plant extracts typically found in biotechnology. Progress in this area of bioseparation thus depends on the input of both the biological and the material sciences. This review tries to give an introduction to affinity precipitation of biologicals from a macro-molecular point of view. The principles and (macro-) molecules currently used to enforce specific precipitation are presented taking recent applications of affinity precipitation as examples.
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