Seite - (000378) - in Biomedical Chemistry: Current Trends and Developments

opsonization by the RES. In addition, the expression of the targeted receptors by nonmalignant tissues may originate unwanted off-target effects, compromising one of the main advantages on using targeting therapy. In order to circumvent the aforementioned bottlenecks, attention has been focused on the synthesis of peptide-based ligands exhibiting smaller molecular sizes and simpler 3D conformation, consequently resulting in higher stability and relatively lower immunogenicity when compared with the majority of the proteins. The identification of new ligand-receptor combinations normally derive from the application of recently developed high-throughput screening techniques and phage/plasmid/bacterial peptide display libraries (Paulo, 2011). The RGD sequence (i.e., arginine-glycine-aspartic acid) has been extensively included in an immense variety of peptides sharing the capability to specifically target the αvβ3 integrin receptors, an endothelial cell surface receptor overexpressed in neovascular endothelial cells (Fass, 2008; Kamaly, 2012; Miele, 2012). Despite the potential and promising application of RGD peptides on the targeting of endothelium of the tumor microvasculature, the expression of the αvβ3 integrin receptor by normal and inflamed tissues limits its clinical translation. In that sense, investigations have been undergoing with the purpose of generating new RGD analogs with improved targeting specificity (Kamaly, 2012; Nembrini, 2011). 3.5.3.2.3.3 Aptamers Nucleic acid-based aptamers are small, single-stranded RNA or DNA oligonucleotides, where the conformational structure can be designed, rendering them the capability of binding antigens with high affinity and specificity (Bellisola, 2012; Pan, 2010). Candidates for targeting a specific receptor have been screened with oligonucleotide libraries using high throughput screening methodologies. The Promising aptamers are subsequently selected and amplified in detriment of the remaining ones. Recently, an in vitro chemical technique denominated “systemic evolution of ligands by exponential enrichment” (SELEX) has been explored for identification of the referred candidates (Wang, 2013). This