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Palmitoylated Peptides: Pam2Cys-peptides and Pam3Cys-peptides.

Pam2Cys-peptides and Pam3Cys-peptides are Palmitoylated Peptides known to activate the immune system through toll like receptors. Short peptide sequences play a major role in immune recognition. A pathogen, such as bacteria or a parasite, is captured when encountered and degraded by specialized antigen presenting cells of the immune system into short peptide sequences known as epitopes. Palmitoylated Peptides can be part of these peptide epitopes. These epitopes are then presented to effector T cells and, if the correct cellular signals are given, can trigger off a cascade of events that eventually induces an immune response. Synthetic peptides including Palmitoylated Peptides have been used for the design of vaccines in the past. If the epitope that is recognized by an antibody or a T cell is known, a vaccine can be designed around this epitope. Palmitoylated peptides that contain dipalmitoyl-S-glyceryl cysteine (Pam2Cys), tripalmitoyl-S-glyceryl cysteine (Pam3Cys) and macrophage-activating lipopeptide (MALP-2) moieties can be used to deliver antigenic peptides that contain toll like receptor (TLR) agonists. Palmitoylated peptides that contain Pam2Cys target the TLR1-2 receptor and palmitoylated peptides that contain Pam3Cys target the TLR2-6 receptor. TLR1 recognizes peptidoglycans and lipoproteins together with TLR2 as a heterodimer and is found on the surface of macrophages and neutrophils. Palmitoylation is a post translational modification in which fatty acids, such as palmitic acid, are attached to cysteine and sometimes to serine and threonine residues of proteins. This modification enhances the hydrophobicity of proteins and contributes to their membrane association. Furthermore, these types of modified peptides appear to be a promis­ing approach for the development of new immunotherapeu­tics. A chemically synthesized tripalmitoyl pentapeptide (TPP) has been shown to be a potent mitogen and polyclonal activator for B lymphocytes of both lipopolysaccharide (LPS)-R and LPS-LR mice. Immunogenicity of vaccine peptides is dependent on how the peptide antigen and adjuvant are recog­nized by the immune system. For the development of a specific pep­tide-based vaccine formulation that is efficiently delivered to its specific target factors such as peptide orientation and structure, stability of peptides against deg­radation and clearance, tissue localization, antigen uptake and processing, and toxic­ity have to be considered. The attachment of a single palmitic acid moiety to an antigenic peptide to form a palmitoylated peptide enhances peptide immunogenicity in a TLR2-dependent manner and the conjugation of antigenic peptides to dipalmitoyl-S-glyceryl cysteine (Pam2Cys) has generated antigen-specific immune responses in a wide variety of animal studies including those evaluating B‑cell epitopes for a contraceptive therapy, Tc‑cell epitopes for hepati­tis C virus, influenza virus, intracellular bacterium Listeria monocytogenes, and the model tumor antigen ovalbumin. Lipid-core peptides linking synthetic analogs of Pam3Cys to multiple peptides via dendrimeric mul­tiple antigen peptide structures have proven to be effective for Group A streptococcal (GAS) vaccines. In addition palmitic acid-based adjuvants using palmitic acid, dipalmitoyl-S-glyceryl-cysteine (Pam2Cys) and tripalmitoyl-S-glyceryl-cysteine (Pam3Cys) lipid moieties have been shown to be effective for epitope-based vaccines and do not exhibit the harmful side effects that are commonly associated with many other adjuvant formulations. This type of vaccine delivery system also allows for the delivery of multiple peptides in one complex. Furthermore, different epitopes that may be needed to achieve broad-spectrum immunity can be included. 

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