Challenges and approaches for assay development of membrane and membrane-associated proteins in drug discovery.
In addition to its role as a barrier between the cytoplasm and the extracellular milieu, the cell membrane is a scaffold for a diverse collection of receptors and enzymes. The organization afforded by this scaffold serves to ensure an efficient interaction between the components of the membrane. The desire to maintain this organization in solution is a challenge for the appropriate interrogation of these biochemical components. This chapter will discuss strategies that allow biochemical analysis of membrane-associated enzymes within standard biochemical reactions. The advantages of these screening strategies in identifying valuable compounds from compound libraries and in understanding the intricacies of complex multiprotein complexes (i.e., chemotaxis) will be discussed.
Gridley
Scott
S
Blue Sky Biotech, Inc, Worcester, Massachusetts, USA.
Shrout
Anthony L
AL
Esposito
Edward A
EA
D000818:Animals; D001419:Bacteria / Q000187:drug effects / Q000378:metabolism; D002633:Chemotaxis; D055808:Drug Discovery / Q000379:methods*; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000187:drug effects* / Q000378:metabolism*; D017955:Poliovirus / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction; D013925:Thromboplastin / Q000187:drug effects / Q000378:metabolism; D053586:Virus Internalization / Q000187:drug effects
D008565:Membrane Proteins; D013925:Thromboplastin; D066246:ErbB Receptors