Molecular dynamics simulations together with experimental studies reveal strong membrane activity of a small peptide

251st American Chemical Society National Meeting & Exposition - Computers in ChemistryCell-penetrating peptides (CPPs) and antimicrobial peptides (AMPs) are generally defined as small cationic peptides with the ability to interact with lipidic membranes, in a process driven by electrostatic and hydrophobic processes. The interaction with CPPs is known to lead to its translocation across the membrane, while with AMPs lead to membrane damage. Here we present one synthetic anionic peptide, which strongly interacts with model membranes, showing properties of the two peptide classes, namely the translocation through lipidic membranes on a mechanism usually described for cationic CPPs and membrane destabilization like AMPs promote. These properties were shown through molecular dynamic studies, experimental studies with liposomes and mammalian cells in vitro. Based on the peptide properties here demonstrated, small modifications in its structure could make it a very promising tool for drug delivery.info:eu-repo/semantics/publishedVersio

Characteristic Temperatures of Folding of a Small Peptide

We perform a generalized-ensemble simulation of a small peptide taking the interactions among all atoms into account. From this simulation we obtain thermodynamic quantities over a wide range of temperatures. In particular, we show that the folding of a small peptide is a multi-stage process associated with two characteristic temperatures, the collapse temperature T_{\theta} and the folding temperature T_f. Our results give supporting evidence for the energy landscape picture and funnel concept. These ideas were previously developed in the context of studies of simplified protein models, and here for the first time checked in an all-atom Monte Carlo simulation.Comment: Latex, 6 Figure

Mimotope mapping as a complementary strategy to define allergen IgE-epitopes: peach Pru p 3 allergen as a model.

Lipid transfer proteins (LTPs) are the major allergens of Rosaceae fruits in the Mediterranean area. Pru p 3, the LTP and major allergen of peach, is a suitable model for studying food allergy and amino acid sequences related with its IgE-binding capacity. In this work, we sought to map IgE mimotopes on the structure of Pru p 3, using the combination of a random peptide phage display library and a three-dimensional modelling approach. Pru p 3-specific IgE was purified from 2 different pools of sera from peach allergic patients grouped by symptoms (OAS-pool or SYS-pool), and used for screening of a random dodecapeptide phage display library. Positive clones were further confirmed by ELISA assays testing individual sera from each pool. Three-dimensional modelling allowed location of mimotopes based on analysis of electrostatic properties and solvent exposure of the Pru p 3 surface. Twenty-one phage clones were selected using Pru p 3-specific IgE, 9 of which were chosen using OAS-specific IgE while the other 12 were selected with systemic-specific IgE. Peptide alignments revealed consensus sequences for each pool: L37 R39 T40 P42 D43 R44 A46 P70 S76 P78 Y79 for OAS-IgE, and N35 N36 L37 R39 T40 D43 A46 S76 I77 P78 for systemic-IgE. These 2 consensus sequences were mapped on the same surface of Pru p 3, corresponding to the helix 2-loop-helix 3 region and part of the non-structured C-terminal coil. Thus, 2 relevant conformational IgE-binding regions of Pru p 3 were identified using a random peptide phage display library. Mimotopes can be used to study the interaction between allergens and IgE, and to accelerate the process to design new vaccines and new immunotherapy strategie