A POLYETHYLENE-GLYCOL COPOLYMER FOR CARRYING AND RELEASING MULTIPLE COPIES OF CYSTEINE-CONTAINING PEPTIDES

Two different methods were developed to prepare an adduct of a poly(et hylene glycol)-lysine copolymer with either cysteamine or 1-amino-2-me thyl-2-propanethiol. Cysteine-containing peptides could then be disulf ide-linked to the thiol groups on the polymer in a facile maimer. In t he described procedures, a coupling ratio of about 8 peptides/molecule of poly(ethylene glycol)-lysine copolymer (M-w = 27 000) was typicall y attained. The products were stable at neutral pH, but the peptides c ould be released from the polymer in a physiologically relevant reduci ng environment. The release rate was highly dependent on the linker us ed for forming the disulfide bond. To illustrate the potential biomedi cal usefulness of this polymer carrier, a Tat peptide-PEG conjugate wa s shown to inhibit expression of a reporter gene fused to the TAR elem ent of human immunodeficiency virus in a model cell assay.