External hydrocephalus after aneurysm surgery: paradoxical response to ventricular shunting

A novel amino acid type poly(ethylene glycol) (aaPEG) was prepared and its application as a drug-carrier was examined. The peptides, Pro-Asp-Ser-Gly-Arg (PDSGR) and Tyr-Ile-Gly-Ser-Arg (YIGSR) which are active fragments of Laminin (a cell adhesion protein), were previously reported to be inhibitors of experimental metastasis. Both peptides were conjugated with aaPEG (average molecular weight, 3,000) to prepare a bifunctional peptide-PEG hybrid. The hybrid, PDSGR-aaPEG-YIGSR, was manually prepared by the solid-phase fluorenylmethyloxycarbonyl (Fmoc) strategy. The antimetastatic activity of the peptides in mice was not lost when conjugated to form a larger aaPEG molecule. YIGSR(375 nmol) and PDSGR (375 nmol and 750 nmol) did not demonstrate antimetastatic activity, but a mixture of PDSGR (187 nnmol) and YIGSR (187 nmol) exhibited an inhibitory effect. The inhibitory effect of the hybrid (187 nmol) was more potent than that of the mixture (PDSGR and YIGSR), indicating that the inhibitory effect of the peptides was potentiated by hybrid formation with aaPEG.