Bioreversible Derivatization of Peptides

  • Hans Bundgaard
Part of the NATO ASI Series book series (NSSA, volume 125)


In recent years several biologically active peptides have been discovered, including peptides consisting of only two or three amino acids, and most certainly, the development of peptide drugs will be a major area in drug research in the future. The application of peptides as clinically useful drugs is, however, seriously hampered due to substantial delivery problems. Peptides are readily degraded by enzymes in the gastrointestinal system and are absorbed poorly, making the oral route a poor way of administration (Wiedhaup, 1981). Pronounced degradation of peptides does also occur at routes of administration other than oral, such as the ocular, nasal, buccal, rectal and vaginal routes (Okada et al., 1982; Kimura, 1984; Lee et al., 1985; Stratford and Lee, 1986). Another factor contributing to the poor bioavailability of peptides is most certainly the non-lipophilicity of peptides. Furthermore, peptides suffer from metabolic lability arising from hydrolysis by plasma and tissue peptidases and even simple parenteric administration is problematic, due to the short half-lives of the peptides once they reach the bloodstream. Several peptides also suffer from systemic transport problems in that they do not readily penetrate cell membranes to reach the receptor biophase or cross the blood-brain barrier (Farmer and Ariëns, 1982; Meisenberg and Simmons, 1983).


Mannich Base Peptide Drug Ester Prodrug Tensin Converting Enzyme Inhibitor Lipophilic Prodrug 
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Copyright information

© Springer Science+Business Media New York 1986

Authors and Affiliations

  • Hans Bundgaard
    • 1
  1. 1.Department of Pharmaceutical Chemistry ADRoyal Danish School of PharmacyCopenhagenDenmark

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