Thirty years of affinity chromatography (original) (raw)

1999, Reactive and Functional Polymers

Affinity chromatography was introduced 30 years ago and is the most powerful tool for purification of biologically active molecules. Affinity chromatography has also had a major impact and virtually revolutionized the entire field of modern biology, molecular biology, biochemistry, medicine and biotechnology. The development of affinity chromatography has led to many other studies and applications in which the concept of molecular recognition and biorecognition is used.

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Affinity Chromatography with Collapsibly Tethered Ligands

Analytical Chemistry, 2003

We introduce a novel affinity chromatography mode in which affinity ligands are secured to the media surface via collapsible tethers. In traditional affinity chromatography, the immobilized ligands act passively, and their local concentration is static. In collapsibly tethered affinity chromatography, the ligand can move dynamically in response to external stimuli, a design that enables marked changes in both the local concentration of the ligand and its surrounding environment without exchange of solvent. Using the thermoresponsive polymer poly(N-isopropylacrylamide) (PIPAAm) as a scaffold for ligand and hapten attachment, we were able to achieve controlled mobility and microenvironment alteration of the affinity ligand Ricinus communis agglutinin (RCA 120). The glycoprotein target, asialotransferrin, was loaded onto a column in which PIPAAm was partially substituted with both RCA 120 and lactose. At 5°C, the column retained the glycoprotein, but released most (95%) of the asialotransferrin upon warming to 30°C. This temperature-induced elution was much greater than can be explained by temperature dependency of sugar recognition by RCA 120. The simplest explanation is that upon thermally induced dehydration and collapse of the PIPAAm chains, coimmobilized RCA 120 ligand and lactose hapten are brought into closer proximity to each other, enabling immobilized lactose to displace affinity-bound asislotransferrin from the immobilized RCA 120 lectin. Affinity chromatography has been used widely in biomedical research and biotechnology. 1 It is based on molecular recognition where one recognition partner is immobilized on a base matrix, and soluble target molecules can be retained from a crude mixture. The target molecule can then be released and recovered in a functional form. The basis of elution is to reduce the affinity between immobilized ligand and analyte. This is most often accomplished by use of a bond-breaking buffer (i.e., by changing

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