Synthesis and evaluation of fluorogenic substrates for phospholipase D and phospholipase C

Org Lett. 2006 Jun 8;8(12):2575-8. doi: 10.1021/ol060773d.

Abstract

Fluorogenic analogues of phosphatidylcholine and lysophosphatidylcholine, DDPB and lysoDDPB, were synthesized by an enzyme-assisted strategy. The analogues were evaluated as substrates for phospholipases C and D and lysophospholipase D. DDPB was cleaved by bacterial and plant phospholipase D (PLD) enzymes and represents the first direct fluorogenic substrate for real-time measurement of PLD activity. Both fluorogenic substrates have potential in screening for PLD and PC-PLC inhibitors and for monitoring spatiotemporal changes in PLD activity in cells. [structure: see text]

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacillus cereus / enzymology
  • Clostridium perfringens / enzymology
  • Enzyme Activation / physiology
  • Fluorescent Dyes / chemical synthesis*
  • Fluorescent Dyes / metabolism
  • Lysophosphatidylcholines / chemical synthesis*
  • Lysophosphatidylcholines / metabolism
  • Phosphatidylcholines / chemical synthesis*
  • Phosphatidylcholines / metabolism
  • Phospholipase D / chemistry*
  • Phospholipase D / metabolism*
  • Phosphoric Diester Hydrolases / metabolism
  • Spider Venoms / enzymology
  • Spider Venoms / metabolism
  • Type C Phospholipases / chemistry*
  • Type C Phospholipases / metabolism*

Substances

  • Fluorescent Dyes
  • Lysophosphatidylcholines
  • Phosphatidylcholines
  • Spider Venoms
  • loxosceles venom
  • Phosphoric Diester Hydrolases
  • Type C Phospholipases
  • Phospholipase D