A Novel Class of Intrinsic Proteasome Inhibitory Gene Transfer Peptides

Overview

Journal Bioconjug Chem

Publisher American Chemical Society

Specialty Biochemistry

Date 2007 Dec 22

PMID 18095640

Citations 4

Authors

Molly E Martin

Kevin G Rice

Affiliations

Soon will be listed here.

Abstract

Proteasomes are multisubunit enzymes responsible for the degradation of many cytosolic proteins. The inhibition of the proteasome has been the subject of intense interest in the development of drug therapies. We have previously demonstrated that simultaneous administration of a tripeptide aldehyde proteasome inhibitor (MG115 or MG132) with a peptide (Cys-Trp-Lys18) DNA condensate boosted gene expression by 30-fold in cell culture. In the present study, we have developed a convergent synthesis to allow the incorporation of a proteasome inhibitor tripeptide into the C-terminal end of a gene delivery peptide. The resulting peptides formed DNA condensates that mediated a 100-fold enhancement in gene expression over a control peptide lacking all or part of the tripeptide inhibitor. Gene transfer peptides possessing intrinsic proteasome inhibitors were also found to be nontoxic to cells in culture. These results suggest that intrinsic proteasome inhibition may also be used to boost the efficiency of peptide-mediated nonviral gene delivery systems in vivo.

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