Page - (000254) - in Biomedical Chemistry: Current Trends and Developments

8 Significance of the N- and C-terminus 9 N-terminal esterification (phosphoester) or pegylation modifications to enhance plasma stability (e.g. resistance to exopeptidases) and to reduce immunogenicity. Pegylation is also designed to make the peptide larger (generally > 50 kDa) to retard excretion through the kidneys (renal clearance) Alternative routes for the administration of peptide-based drugs have been improved in recent years and novel peptide delivery technologies have emerged, including controlled-release parental drug, mucosal route, oral route and transdermal route (Pettit & Gombotz, 1998). In spite of some limitations, synthetic therapeutic peptides present numerous advantages compared with their homologous compounds (proteins and antibodies) and with small organic molecules, thanks to progress in chemical synthesis and routes of administration (Vlieghe, 2010). In Table 3.1.5, the principal advantages of peptides over proteins/antibodies or over small organic molecules that make up traditional medicines are presented. Table 3.1.5: Advantages of peptides over other drug candidates as proteins/antibodies or organic molecules (Loffet, 2002; Lien & Lowman, 2003; Witt & Davis, 2006; Vlieghe, 2010; McGregor, 2008; Hummel, 2006). Proteins and antibodies Organic molecules Peptides have the potential to penetrate further into tissues owing to their smaller size and charge Therapeutic peptides are generally less immunogenic than recombinant proteins and antibodies Lower manufacturing costs (synthetic vs. recombinant production) Higher activity per unit mass Organic molecules often represent the smallest functional part of a protein, offering greater efficacy, selectivity and specificity The degradation products of peptides are amino acids (minimizing the risks of systemic toxicity or drug-drug interactions Because of their short half-life, few peptides accumulate in tissues (reduction of risks of complications caused by their metabolites)