Improved stability and selectivity of lytic peptides through self-assembly.
Widespread clinical applications of peptide drugs have been hindered by their low stability and selectivity. Peptides can be easily digested by various enzymes in the blood and thus show a short life-span. Meanwhile, peptide drugs can cause severe normal tissue damage due to their low selectivity. Therefore, for effective therapy, a high dosage of peptide is required which is usually in excess of the clinically and economically acceptable level. In this study, we have tried to design new lytic peptides which can self-assemble into peptide fibrils with defined nanostructures as observed under atomic force microscopy. Lytic peptides in self-assembled peptide fibrils will lose their cell lysis activity but become resistant to enzyme degradation. Such lytic peptide self-assembly has proven to be a reversible process which is controlled by surrounded environments. A concentration controlled sustained release of free and active lytic peptide from self-assembled peptide fibrils has been achieved. Self-assembled lytic peptides with enzyme resistance, sustained release, and prodrug feature may have great clinical application potentials.
Department of Chemistry and Chemical Biology, Stevens Institute of Technology, Castle Point on Hudson, Hoboken, NJ 07030, USA.
Zhigang
Z
Tu
Jumin
J
Hao
Riddhi
R
Kharidia
Xiao G
XG
Meng
Jun F
JF
Liang
D000595:Amino Acid Sequence; D002478:Cells, Cultured; D006801:Humans; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D008969:Molecular Sequence Data; D049329:Nanostructures / Q000737:chemistry; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D017433:Protein Structure, Secondary
C524354:PTP-7S peptide; D010446:Peptide Fragments; D010455:Peptides