A Mass Spectrometry Screening Method for Antiaggregatory Activity of Proteins Covalently Modified by Combinatorial Library Members: Application to Sickle Hemoglobin

A homogeneous assay, based on electrospray mass spectrometry, is described for identifying compounds in a combinatorial library that covalently modify a protein and thereby enhance its solubility. The technique is based on measuring the distribution of modified proteins in the supernatant versus aggregate. Compounds having the greatest anti-aggregatory activity are those with the highest supernatant/aggregate ratio. Mass is used as a marker to...