Non-invasive peptide delivery routes such as oral, buccal, nasal, pulmonary and transdermal offer several advantages including safety and ease of use for the patient, and the potential for increased physician acceptance and patient compliance for chronic indications. Oral delivery remains the most extensively studied non-invasive route, but it presents numerous biological challenges. Of the few oral peptides currently marketed, most are intended for localized intestinal delivery or represent peptides with special characteristics. Absorption of orally delivered peptides into the systemic circulation generally occurs in the duodenum or lower regions of the small intestine. The intestinal epithelium and the mucus layer offer a barrier to the transport of molecules greater than 2 to 3 amino acids in size, and intestinal proteolytic enzymes derived either from the pancreas or from the intestinal brush border membranes rapidly cleave peptide bonds. For most peptides, these challenges of poor intestinal permeability, susceptibility to proteolytic degradation, as well as their short half-life, propensity to aggregate, and other limitations need to be overcome by formulation or peptide structure modifications to increase bioavailability and develop commercially successful products. Strategies such as cyclization, addition of unnatural amino acids, and blocking of N- and C-termini to stabilize peptides and increase their protease resistance, are examples of beneficial structural modifications. The addition of protease inhibitors and permeation enhancers to the formulation, conjugation to peptide transporters, and encapsulation in robotic pills or micro- and nano-spheres are also widely used techniques. However, further increases in bioavailability, decreases in inter- and intra-patient variability, elimination of food effects, and confirmation of long term safety of formulation excipients remain as foci for further efforts to fully realize the potential for oral delivery. A variety of peptide molecules are currently in pre-clinical or different stages of clinical development using one or more of these technologies to facilitate paracellular or transcellular transport, and recent data on these studies will be presented.

Solid phase peptide synthesis is normally following the four stages: synthesis, global deprotection, purification and freeze-drying and isolation. Among them, the purification crude peptide is very challenging because of the following difficulties: small loading amounts, long separation time, poor recoveries and that leads to high costs. Moreover, crude synthetic peptides contain impurities with retention characteristics very similar to the target peptide which can present additional purification challenge. In addition, hydrophobic peptides can pose greater challenges when these peptides have low solubility in both aqueous and organic solvents. Although synthesis and purification of short-peptides is strait forward, the synthesis and purification of longer peptides is problematic because of poor solubility in the solvent used both in reverse-phase and normal phase chromatography.

Short peptides have attracted an increasing interest due to their wide applications, inter alia in anticancer therapy or supramolecular biofunctional materials [1-3]. Amino acids and peptides in living systems, whose architecture is controlled by non-covalent interactions, have a valuable input in understanding highly complex biological processes. Supramolecular interactions in precise co-operation just like virtuosos play a symphony of life. Supramolecular chemistry of biomolecules is crucial in interpretation of biological phenomena. Design of smart bio-materials or drugs should be based on the knowledge of weak interactions at molecular and higher topological level. Nevertheless, the detailed knowledge on this subject is still challenging. The concept of supramolecular synthons, recurring patterns of inter-contacts between functional groups, is useful in small supramolecules and in understanding of the interplay of biocomplexes (ligand–protein cocrystals, between different scaffolds in the ligand molecules and the main/side chain of proteins in the active sites). This e-poster focuses on synthesis and supramolecular crystallography of linear and cyclic short peptides, supported by theoretical methods, taking a holistic look at their landscape in the context of subtle supramolecular effects on the basis of our own research and those form the databases (CSD/PDB). The aim is to present the potential uses of supramolecular synthon idea, which evolves in various fields in an intriguing manner, in relation to short peptides. Novel biologically important synthons, e.g. created by weak cyclopropyl or Fmoc-synthons, will be discussed in detail. We hope that our study will contribute to the development of supramolecular chemistry of peptides and also in protein recognition or development of advanced therapeutic approaches.