Environmental Effects Dominate the Folding of Oligocholates in Solution, Surfactant Micelles, and Lipid Membranes

Oligocholate foldamers with different numbers and locations of guanidinium−carboxylate salt bridges were synthesized. The salt bridges were introduced by incorporating arginine and glutamic acid residues into the foldamer sequence. The conformations of these foldamers were studied by fluorescence spectroscopy in homogeneous solution, anionic and nonionic micelles, and lipid bilayers. Environmental effects instead of inherent foldability were found to dominate the folding. As different noncovalent forces become involved in the conformations of the molecules, the best folder in one environment could turn into the worst in another. Preferential solvation was the main driving force for the folding of oligocholates in solution. The molecules behaved very differently in micelles and lipid bilayers, with the most critical factors controlling the folding−unfolding equilibrium being the solvation of ionic groups and the abilities of the surfactants/lipids to compete for the salt bridge. Because of their ability to fold into helices with a nonpolar exterior and a polar interior, the oligocholates could transport large hydrophilic molecules such as carboxyfluorescein across lipid bilayers. Both the conformational properties of the oligocholates and their binding with the guest were important to the transport efficiency.Reprinted (adapted) with permission from Journal of the American Chemical Society 132 (2010): 9890, doi:10.1021/ja103694p. Copyright 2010 American Chemical Society.</p

Efficacy of co-immunization with the DNA and peptide vaccines containing SYCP1 and ACRBP epitopes in a murine triple-negative breast cancer model

Multiepitope cancer vaccines have gained lots of attention for prophylactic and therapeutic purposes in cancer patients. In our previous study, multiepitope DNA and peptide cancer vaccines consisted of the most immunodominant epitopes of ACRBP and SYCP1 antigens were designed by bioinformatic tools. In this study, the effect of prophylactic co-immunization with these DNA and peptide cancer vaccines in the 4T1 breast cancer animal model was assessed. Serum levels of the peptide-specific IgG total, IgG2a and IgG1 were measured by enzyme-linked immunosorbent assay (ELISA). Also, the efficacy of the immunized mice splenocytes’ for producing interleukin-4 (IL-4) and interferon-γ (IFN-γ) was evaluated. The co-immunization caused a significant (P < .05) increase in the serum levels of IgG1 and IgG2a. The co-immunized mice splenocytes exhibited significantly enhanced IL-4 (6.6-fold) and IFN-γ (19-fold) production. Also, their lymphocytes exhibited higher proliferation rate (3-fold) and granzyme B production (6.5-fold) in comparison with the control. The prophylactic co-immunization significantly decreased the breast tumors’ volume (78%) and increased the tumor-bearing mice survival time (37.5%) in comparison with the control. Taking together, prophylactic co-immunization with these multiepitope DNA and peptide cancer vaccines can activate the immune system against breast cancer. However, further experiments are needed to evaluate their efficacy from different angles