Page - (000243) - in Biomedical Chemistry: Current Trends and Developments

CPPs differ from most other peptides with respect to specific features that reflect various mechanisms used to enter the cell (Milletti, 2012). Cell-penetrating peptides (CPPs) are relatively short peptides that consist of less than 40 amino acids, are able to enter cells by means of various mechanisms, including endocytosis, and are able to assist in the further intracellular delivery of covalently or noncovalently conjugated bioactive cargos (Heitz, 2009; Vale, 2016), as illustrated in Fig. 3.1.12. Figure 3.1.12: The structure of a drug-linker-peptide (CPP) conjugate developed in our research group. X and Y represent the common functional groups used to connect either the drug or the peptide to the linker. X may be similar to or different than Y. Here, the nature of the X bond and the drug peptide conjugation chemistry has been classified according to the nature of the X bond: a) disulfide bond, b) amide, c) thioether, d) carbamate ester, e) carboxylic acid ester or f) hydrazone bond. Sequences of common CPPs are provided in Table 3.1.2. The common virtue of all CPPs is the ability to efficiently pass through cell membranes while carrying a wide variety of cargos inside cells (Fig. 3.1.13) (Capolovici, 2014). Interestingly, CPP sequences are known to vary considerably as seen by examining Table 3.1.2. There are, however, several similarities between the structural natures of these short