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(ethylene glycol)-lysine copolymer with either cysteamine or 1-amino-2-methyl-2-propanethiol. Cysteine-containing peptides could then be disulfide-linked to the thiol groups on the polymer in a facile manner. In the described procedures, a coupling ratio of about 8 peptides/molecule of poly(ethylene glycol)-lysine copolymer (Mw = 27 000) was typically attained. The products were stable at neutral pH, but the peptides could be released from the polymer in a physiologically relevant reducing environment. The release rate was highly dependent on the linker used for forming the disulfide bond. To illustrate the potential biomedical usefulness of this polymer carrier, a Tat peptide-PEG conjugate was shown to inhibit expression of a reporter gene fused to the TAR element of human immunodeficiency virus in a model cell assay.
Huang
S Y
SY
Center for Advanced Biotechnology and Medicine and Chemistry Department, Rutgers University, New Brunswick, New Jersey 08903-2101, USA.
Pooyan
S
S
Wang
J
J
Choudhury
I
I
Leibowitz
M J
MJ
Stein
S
S
D019921:Biotinylation; D003543:Cysteamine / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism*; D004220:Disulfides / Q000737:chemistry; D016503:Drug Delivery Systems; D015870:Gene Expression / Q000187:drug effects; D015696:Gene Products, tat / Q000378:metabolism; D017930:Genes, Reporter / Q000235:genetics; D005978:Glutathione / Q000378:metabolism; D016325:HIV Long Terminal Repeat / Q000235:genetics; D006801:Humans; D019169:Jurkat Cells; D007700:Kinetics; D008239:Lysine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010455:Peptides / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011725:Pyridines / Q000378:metabolism; D013053:Spectrophotometry; D013438:Sulfhydryl Compounds / Q000378:metabolism
D004220:Disulfides; D015696:Gene Products, tat; D010455:Peptides; D011725:Pyridines; D013438:Sulfhydryl Compounds; C092361:poly(ethylene glycol) lysine copolymer; D011092:Polyethylene Glycols; D003543:Cysteamine; C029347:2-thiopyridine; D005978:Glutathione; D008239:Lysine; D003545:Cysteine