Targeting specific PDZ domains of PSD-95; structural basis for enhanced affinity and enzymatic stability of a cyclic peptide.

@article{Piserchio2004TargetingSP,
  title={Targeting specific PDZ domains of PSD-95; structural basis for enhanced affinity and enzymatic stability of a cyclic peptide.},
  author={Andrea Piserchio and Gregory D Salinas and Tao Li and John Marshall and Mark R Spaller and Dale F. Mierke},
  journal={Chemistry & biology},
  year={2004},
  volume={11 4},
  pages={469-73}
}
A cyclic peptide, Tyr-Lys-c[-Lys-Thr-Glu(betaAla)-]-Val, incorporating a beta-Ala lactam side chain linker and designed to target the PDZ domains of the postsynaptic density protein 95 (PSD-95), has been synthesized and structurally characterized by NMR while free and bound to the PDZ1 domain of PSD-95. While bound, the lactam linker of the peptide makes a number of unique contacts outside the canonical PDZ binding motif, providing a novel target for PDZ-domain specificity as well as producing… CONTINUE READING