Cellular Delivery of Functional Peptides to Block Cytokine Gene Expression

Details

• Personal Author:
  Antonini JM ; Luo Q ; Rojanasakul Y ; Toledo D ; Ye J
• Description:
  Advances in molecular and cellular biology have identified the cellular mediators that regulate many disease processes and have facilitated the development of new therapeutic agents that control these events. However, the size, complexity, and cellular inaccessibility of these therapeutic agents make their cellular delivery difficult. Here, we describe an efficient cellular delivery system that exploits the membrane-translocating ability of signal peptides to import functional peptides into cells. Molecular conjugates consisting of the signal import peptide (IP) and nuclear localization sequence (NLS) of the transcription factor NF-kappaB were synthesized. Electrophoretic mobility shift and enzyme-linked immunosorbent assays were used to assess the inhibitory effects of these synthetic peptides on agonist-induced NF-kappaB nuclear translocation and transcriptional activation. Our results indicated that the peptides were effective in inhibiting both the nuclear translocation and transcriptional activation of NF-kappaB. However, their effects required the presence of the IP moiety for efficient cellular entry of the NLS. Structural analysis of IP showed that the hydrophobic domain, and to a lesser extent the N-terminal domain, was responsible for the membrane translocating activity of IP. [Description provided by NIOSH]
• Subjects:
  Genetics Occupational Health Safety
• Keywords:
  Author Keywords: Peptide Cellular Function Genes Molecular Biology NF-kB Peptides Therapeutic Agents TNFa Transcription Factor Transport
• ISSN:
  0168-3659
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; Pennsylvania ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  13-17
• Volume:
  65
• Issue:
  1
• NIOSHTIC Number:
  nn:20020795
• Citation:
  J Control Release 2000 Mar; 65(1-2):13-17
• Contact Point Address:
  Department of Basic Pharmaceutical Sciences, West Virginia University, School of Pharmacy, PO Box 9530, Morgantown, WV 26506, USA
• Email:
  yrojanasakul@hsc.wvu.edu
• Federal Fiscal Year:
  2000
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Controlled Release
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d50b0e31e3395949b105f40fdd7d22e51a98bce64274b9ed3540a6442be00c835cb96477b529537a6ef9433c0a6b106ac7657375ebb20a76b6c9bd37bad34995
• Download URL:
  https://stacks.cdc.gov/view/cdc/198461/cdc_198461_DS1.pdf
• File Type:
  [PDF - 303.14 KB ]