Transduction Peptides Research Articles

Transduction peptides: from technology to physiology.

During the past fifteen years, a variety of peptides have been characterized for their ability to translocate into live cells. Most are efficient vectors that can internalize hydrophilic cargoes, and so provide a valuable biological (and potentially therapeutic) tool for targeting proteins into cells. Furthermore, translocation of cell-permeable peptides across the plasma membrane and their subsequent access to the cytosol, even when fused to large hydrophilic proteins, is challenging the perception of the plasma membrane as an impermeable barrier.

Identification of a synovial fibroblast-specific protein transduction domain for delivery of apoptotic agents to hyperplastic synovium

Synovial hyperplasia, resulting in erosion of cartilage and bone, represents one of the major pathologies associated with rheumatoid arthritis. To develop an approach for efficient delivery of proteins or agents to synovium to induce targeted apoptosis of hyperplastic synovial tissue, we have screened an M13 peptide phage display library for synovial-specific transduction peptides. We identified a novel synovial-targeted transduction peptide, HAP-1, which is able to facilitate specific internalization of protein complexes into human and rabbit synovial cells in culture and rabbit synovial lining in vivo. HAP-1 and a non-tissue-specific cationic protein transduction domain, PTD-5, were fused to an antimicrobial peptide, (KLAK)2, to generate two proapoptotic peptides termed DP2 and DP1, respectively. Administration of these peptides was able to induce apoptosis of rabbit and human synovial cells in culture, with DP2 inducing synovial cell-specific apoptosis. Intra-articular injection of DP1 and DP2 into arthritic rabbit joints with synovial hyperplasia induced extensive apoptosis of the hyperplastic synovium, while reducing the leukocytic infiltration and synovitis. These results suggest that proapoptotic peptides and, in particular, DP2 can be clinically useful for treatment of synovial hyperplasia, as well as inflammation. Moreover, the results demonstrate the feasibility of identifying tissue-specific transduction peptides capable of mediating efficient transduction in vivo.

The adaptive effects of hypoxic preconditioning of brain neurons.

Prophylactic transient hypoxia (preconditioning) increased neuron resistance to subsequent induction of severe hypoxia. Published data and results obtained by the authors on the molecular-cellular mechanisms of hypoxic preconditioning are presented. The roles of intracellular signal transduction, genome function, stress proteins, and neuromodulatory peptides in this process are discussed. The roles of glutamatergic as well as calcium and phosphoinositide regulatory systems and neuromodulatory factors as components of "volume" signal transmission are analyzed in hypoxic preconditioning-associated induction of functional tolerance mechanisms against the acute harmful effects of hypoxia on neurons in olfactory slices.

Preparation of Nα-Boc 4-O-Diethylphospho-L-azatyrosine, a Regent Potentially Useful for the Synthesis of Signal Transduction Related Peptides

Preparation of the phosphorylated azatyrosine analogue, 2(S)-Nα-Boc-3-[5’-(diethyl phosphoryloxy)-2’-pyridyl]propionate (3), is reported. This compound is designed for the solid-phase synthesis of cell signal transduction peptides containing a phosphotyrosyl reside bearing a nitrogen atom in the tyrosyl aromatic ring. An important aspect of the synthetic approach is the use of diethyl phosphate functionality for phenolic hydroxyl protection during palladium-mediated coupling.