The presence of DNase and protease activity in serum can lead to partial degradation of the carrier polyarginine peptide, whereas the unnatural PNA backbone was reported to be very stable to enzymatic degradation in this medium.
Recently, a novel type of CpG ODN called the P class, which has two palindromic motifs with a PTO backbone, was reported to show higher potential to produce IFN-α and activate NF-κB [ 15].
The lipid A molecular shape and the tilt angle of the backbone sugars are reported to be the complete determinants of endotoxic activity [ 102, 104].
However, the PTO backbone has been reported to cause unwanted side effects such as unspecific binding to various proteins [ 19] and renal damage [ 20].
The attachment of N-glycans to a peptide backbone has been reported to assist in protein folding, stability, solubility, oligomerization, quality control, sorting, and transport [ 20, 21].
Several useful chemical modifications of ODN backbones have been reported to achieve improved resistance to nuclease digestion and prolonged in vivo half-life.
Inclusion of 2'- O-methyl RNA and 2'-fluoro ribose moieties, use of locked nucleic acid siRNA derivatives and incorporation of phosphorothioate backbone modifications have been reported to improve siRNA efficacy [ 23- 26].
The major plasma membrane phospholipids, phosphatidylcholine (PC) and phosphatidylethanolamine (PE) with C16 and C18 acylation of the sn-1 and sn-2 positions of the glycerol backbone, respectively, have been reported to be transported to the plasma membrane independently of the vesicular secretory pathway [ 8, 9].
Syntheses of the octadentate ligands 3,4,3-LI-IAM-1,2-HOPO and 3,4,3-LI-1,2-HOPO-IAM, where the chromophores are attached to different positions in the (LI = linear) spermine backbone, are reported in addition to a tetradentate ligand based on 1,5-diaminopentane.
Therefore, various synthetic methodologies have been reported to access these backbones.
In previous studies, T. brucei procyclic form SM species were reported to contain ceramide backbones (Richmond et al., 2010; Sutterwala et al., 2008).
