MMP-3→Isoquinolines→Nuclear Proteins→Thymine Nucleotides→poly-ADP-ribose

• 18029177(MMP-3): A novel series of highly selective inhibitors of MMP-3.

  The design and synthesis of a series of highly selective hydroxamate inhibitors of stromelysin-1 (MMP-3) is described.

• 18409175(Isoquinolines): On the way to selective PARP-2 inhibitors. Design, synthesis, and preliminary evaluation of a series of isoquinolinone derivatives.

  Among them , we identified the 5-benzoyloxyisoquinolin-1 (2 H) - one derivative as the most selective PARP-2 inhibitor reported so far , with a PARP-2 / PARP-1 selectivity index greater than 60.

• 10364231(Nuclear Proteins): PARP-2, A novel mammalian DNA damage-dependent poly(ADP-ribose) polymerase.

  We propose to call this enzyme poly (ADP-ribose) polymerase 2 (PARP-2).

• 8416979(Thymine Nucleotides): Poly(ADP-ribose) polymerase stimulates DNA polymerase alpha by physical association.

  Furthermore , stimulation by poly (ADP-ribose) polymerase could not be attributed to its DNA-binding function alone since its fragment , containing only the DNA-binding domain , could not exert full stimulatory effect on DNA polymerase , as of the intact enzyme.

• 8021488(poly-ADP-ribose): Poly ADP-ribosylation of a 90-kDa protein is involved in TNF-alpha-mediated cytotoxicity.

  Analysis of ADP-ribose residues by phosphodiesterase hydrolysis showed that the 90-kDa protein was modified by poly ADP-ribosylation.