Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 318, Issue 4, Pages 949-954Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2004.04.121
Keywords
intracellular; delivery; in vivo; peptide; tat; protein kinase C; intracellular signaling; biodistribution
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Funding
- NHLBI NIH HHS [HL52141] Funding Source: Medline
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Intracellularly acting peptide modulators of signaling enzymes provide a powerful means to regulate signaling events. Delivery of peptides into cells is facilitated by conjugation to carrier peptides, such as Tat. When peptides are irreversibly conjugated to Tat, Tat-mediated subcellular localization may predominate, resulting in mislocalization of the peptide cargo. We have used intracellularly acting peptides, conjugated to Tat by a disulfide bond, to modulate protein kinase C (PKC) signaling; these PKC-modulating peptides are released from Tat upon intracellular delivery. Previously, the distribution of these peptides within tissue and throughout the body had not been demonstrated. We show here intravascular delivery of a PKC-peptide, reversibly conjugated to Tat, resulted in distribution throughout cardiac tissue. In addition, a single injection resulted in selective modulation of PKC activity in many organs. Therefore, intracellularly acting peptide modulators of signaling enzymes, reversibly conjugated to Tat, have extensive biodistribution and can be used to modulate signaling pathways in vivo. (C) 2004 Elsevier Inc. All rights reserved.
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