Pseudo–peptides in Drug Discovery

Peptides are among the most versatile bioactive molecules, yet the do not make good drugs, because they are quickly degraded or modified in the body.

Thus, drug discovery has turned to the novel field of peptidomimetics, i.e. to design non–peptide compounds mimicking the pharmacophore and thus the activity of the original peptide. These novel compounds open up new perspectives in drug design by providing an entire range of highly specific pharmaceuticals that have a high bioavailability.

In particular, the following classes of pseudo–peptides are introduced and examined with regard to their chemical properties, pharmacological activity, as well as practical aspects of synthesis:

Oligo–glycines Beta–peptides Gamma–peptides Pyrrole–imidazole polyamides DNA–like peptide nucleic acids Alpha–helical peptide nucleic acids DNA–cleaving pseudo–peptides

The first work drawing together knowledge gained on different types of pseudo–peptides with drug properties, this book is an essential resource for drug devel opers and bioorganic chemists working with those compounds.

Preface.

List of Contributors.

1. Versatile Oligo(N–Substituted) Glycines: The Many Roles of Peptoids in Drug Discovery (J. Patch, et al.).

2. ß–Peptides, y–Peptides and Isosteric Backbones: New Scaffolds with Controlled Shapes for Mimicking Protein Secondary Structure Elements (G. Guichard).

3. Regulation of Gene Expression with Pyrrole–Imidazole Polyamides (P. Dervan, et al.).

4. Peptide Nucleic Acid (PNA):  A Pseudo–peptide with DNA–like Properties (P. Nielsen, et al.).

5. a–Helical Peptide Nucleic Acids (aPNAs) (P. Garner, et al.).

6. DNA and RNA–cleaving Pseudo–peptides (A. Scarso & P. Scarso).

Subject Index.

Peter E. Nielsen has been affiliated with the University of Copenhagen (Denmark) since 1980, and he became full professor at the Department of Medical Biochemistry and Genetics in 1995. He is one of the inventors of peptide nucleic acid (1991), and has further studied and developed this DNA mimic during the last 12 years. In 1998 he co–founded Pantheco A/S (now Santaris A/S), a small biotech company based in Denmark. Peter Nielsen is the co–author of more than 275 scientific papers and 30 patents and patent applications. He received his Ph.B. in 1980 from the University of Copenhagen and an honoroary doctoral degree in 1990. He has also received several scientific awards and is a member of EMBO.

" thoughtfully compiled and well–presented. Researchers working in these specific areas will want to own a copy of this book " ( Journal of the American Chemical Society, February 23, 2005)

"Researchers and students will welcome this book, which will be very useful for collections in pharmacology, bioorganic chemistry, molecular biology, and related fields." (E–STREAMS, February 2005)

"...the editor of this book has brought together a number of excellent reviews for obtaining up–to–date information in the areas of research covered, and I highly recommend it." (Journal of Medicinal Chemistry, 2005, Vol. 48, No. 8)

"In view of the thoroughly up–to–date coverage of the topics in this book, it can be highly recommended for drug developers and bioorganic chemists working with pseudopeptides, and for all researchers who are interested in the field of nucleic acid chemistry." (Angewandte Chemie, Volume 43, Oct. 2004)

"Das Buch stellt die wichtigsten Eigenschaften und die Vielseitigkeit der Pseudopeptide heraus, mit dem Ziel, neue Entwicklungen in der Wirkstoff–Forschung einzuleiten. Angesichts der aktuellen und detaillierten Darstellung der Themen kann die Lekture ohne Einschrankung jedermann empfohlen werden, der in der Wirkstoff–Forschung tatig ist, sich mit Pseudopeptiden beschaftigt oder sich fur die DNA–Forschung interessiert." (Kiyohiko Kawai, Institute od Scientific and Industrial Research, Universitat Osaka, Angewandte Chemie, 2. Novemberheft 2004–116/42 und Angewandte Chemie International Edition, 2nd November Issue 2004–43/42)