On the immunogenic properties of retro-inverso peptides. Total retro-inversion of T-Cell epitopes causes a loss of binding to MHC II molecules

The partial retro–inverso modification: A road traveled together

“…Fusion of membrane-penetrating peptides such as polyArg, the hexadecapeptide derived from the Drosophila Antennapedia homeobox (Antp), and the undecapeptide derived from the HIV-TAT [47][48][49][50][51][52][53][54][55][56][57] to the cargo molecules frequently enables their internalization. Very often the proteolytic susceptibility of these membrane-penetrating peptides compromises their successful application as molecular tools and drug carriers.…”

“…53 Importantly, retro-inversion of peptides presenting potent T-cell epitopes causes a loss of their ability to bind to MHC II molecules and turns them into poor immunogens. 54 Therefore, a combination of resistance to proteolysis, good membrane-penetrating capacity, and lack of immunogenicity and antigenicity makes the RI membrane-penetrating peptides into important potential molecular delivery vehicles. Linking the RI protein transduction domain (PTD)-4, an optimized analog of HIV-TAT [47][48][49][50][51][52][53][54][55][56][57], to a PNA antisense for the AUG translation initiation region of prepro-oxytocin mRNA generated a powerful antisense reagent.…”

“…54 Therefore, a combination of resistance to proteolysis, good membrane-penetrating capacity, and lack of immunogenicity and antigenicity makes the RI membrane-penetrating peptides into important potential molecular delivery vehicles. Linking the RI protein transduction domain (PTD)-4, an optimized analog of HIV-TAT [47][48][49][50][51][52][53][54][55][56][57], to a PNA antisense for the AUG translation initiation region of prepro-oxytocin mRNA generated a powerful antisense reagent. 55 This conjugate was effectively internalized by cultured cerebral cortex neurons and markedly reduced levels of mRNA coding for prepro-oxytocin and the expression of prepro-oxytocin in oxytocin-producing magnocellular neurons from the hypothalamic supraoptic nucleus.…”

“…Internalization and inhibition of growth in mammary cancer cells MCF-7, colon cancer cells (HCT-116), and human peripheral blood lymphocytes stimulated by phytohemoglobin, and reduction in c-Myc transcriptional activity was achieved by a RI Antp-H1-S6A,F8A. This hybrid was com- Recently, Snyder and coworkers reported the restoration of endogenous p53 activity by a RI hybrid of p53CЈ (human p53[361-382]) and TAT-HIV [47][48][49][50][51][52][53][54][55][56][57] linked through their C-and N-terminals, respectively, to a spacing Gly residue ( Figure 11A). 58 In cancer cells, p53CЈ peptide can induce apoptosis by activating endogenous p53 and by restoring function to several p53 DNA contact mutants.…”

“…This study reported that RI p53[361-382]-Gly-TAT-HIV [47][48][49][50][51][52][53][54][55][56][57] permeates into the cells, induces cell cycle arrest ( Figure 11B), transcriptionally activates p53-responsive genes, inhibits tumor cell proliferation in a p53-dependent manner, inhibits the growth of distant solid tumors in immune competent mice ( Figure 11C), and extends the survival of mice harboring either terminal peritoneal carcinomatosis or terminal peritoneal lymphoma ( Figure 11D). In summary, the delivery of permeable proteolytically stable RI p53[361-382]-Gly-TAT-HIV [47][48][49][50][51][52][53][54][55][56][57] is potently activating the p53 tumor suppressor pathway, thus offering an effective treatment for multiple preclinical cancer models. 58 Ramanathan and coworkers reported an interesting strategy to enhance intestinal absorption of large peptides by targeting the sodium-dependent multivitamin transporter (SDMT) as a cellular entry site for oral delivery of biotinylated RI peptides.…”