Page - (000258) - in Biomedical Chemistry: Current Trends and Developments

excess of reagents, since it significantly complicates the necessary purifications. Following a SPPS strategy, the synthesis is significantly less time consuming as there is no need to isolate the synthetic intermediates. The global yield also increases, since the whole process is performed in the same reaction vessel and the use of surplus reagents is admissible as they are later removed by washing and filtration of the peptidyl-resin contained in the vessel, which is usually attached to a vacuum filtration system. The progression of peptide compounds into clinical therapy goes along with the increasing need for new therapeutic strategies due to the limitations of current biomaterials for engineering complex tissues. The chemical synthesis of peptides enables the conjugation of other small molecules or incorporation of non-natural amino acids by design. Conjugation of small molecules to a peptide opens up the possibility for greater chemical diversity, analogous to small-molecule medicinal chemistry approaches for developing high-affinity, high-specificity molecular recognition increasing the range of potential applications of these molecules in the growing area of tissue engineering. Although the interaction of CPPs with cellular membranes often determines their uptake efficiency, CPPs are first and foremost delivery vectors. This means that they must efficiently deliver various cargo molecules to their designated location, whether it is in the cytoplasm or nucleus. CPPs were discovered 20 years ago based on the potency of several proteins to enter cells. In recent years CPPs have been associated with biodistribution and efficacy of oral biodrug delivery. Nevertheless, the recent progress of CPPs as new carriers for intracellular cargo delivery were focused in tumor cells, where only small quantity of drugs were used as cargo. We propose that new methodologies will be used to design and develop CPP-drug complexes, in that CPPs transport their cargo inside cells using endocytosis. Each modification will be carefully designed to avoid problems that could lead to low synthetic yields, poor solubility, aggregation or toxicity. The in vivo delivery of drugs (as cargo) requires a longer drug circulation time, which in turn requires a more stable complex between the CPP and its drug, as it introduces different hydrophilic groups to an already cell-permeable peptide. When using CPPs as a delivery system, one must consider that drug delivery must