NR AJFF
AU Park,S.; Wanna,L.; Johnson,M.E.; Venton,D.L.
TI A mass spectrometry screening method for antiaggregatory activity of proteins covalently modified by combinatorial library members: application to sickle hemoglobin.
QU Journal of Combinatorial Chemistry 2000 Jul-Aug; 2(4): 314-7
PT journal article
AB 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 identify which covalent modifier in the library is involved. An exploratory study is presented which demonstrates that the antisickling activity of a family of isothiocyanates, as measured by the standard C(sat) assay, correlates well (r(2) = 0.98) with the mass spectrometry analysis of the supernatant/aggregate distribution. The technique has potential for screening libraries capable of covalently modifying other proteins of clinical interest, e.g., Alzheimer's, Huntington's, and various prion related diseases.
MH Antisickling Agents/*chemical synthesis/chemistry/pharmacology; Drug Design; Hemoglobin, Sickle/*chemistry; Human; Isothiocyanates/*chemical synthesis/*chemistry/pharmacology; Spectrum Analysis, Mass/methods; Structure-Activity Relationship; Support, U.S. Gov't, P.H.S.
AD Department of Medicinal Chemistry and Pharmacognosy and Center for Pharmaceutical Biotechnology, College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Chicago, Illinois 60612, USA
SP englisch
PO USA