Introduction - Peptide and Protein Design for Biopharmaceutical Applications - page 2

describe the concept of retroinverso structures and deliver an extensive
overview of backbone modifications, before discussing side-chain con-
straints. They describe peptoids and secondary structure mimetics - a
topic that is taken up again in Chapter 6 - as well as topomimetics. An
important aspect of Chapter 3 is the examples given of modifications of
peptide hormones, especially of somatostatin, as peptidomimetics. The
chapter also covers a range of protease inhibitors.
Chapter 4, 'Design of Cyclic Peptides', by Oliver Demmer, Andreas O.
Frank and Horst Kessler, provides a comprehensive overview of its topic.
It starts with naturally-occurring cyclic peptides (cyclosporin A, for
example) and moves on to different ways of cyclizing peptides. Then
some backbone modifications are discussed, a theme covered in
Chapter 3, as well as other modifications of cyclic peptides. A central
part of the chapter is a description of the conformation and dynamics of
cyclic peptides, especially the reduction in conformational space. The
authors describe turn structures in cyclic peptides and concepts in the
rational design of cyclic peptides, leading to the outline of a general
strategy for finding active hits. The text exemplifies this with the
development of the peptide drug candidate Cilengitide as an integrin
inhibitor and CXCR4 antagonist.
Chapter 5, 'Carbohydrates in Peptide and Protein Design', by Jesper
Brask and the editor, describes how carbohydrates are used to intro-
duce new structural and conformational features to peptides and
proteins. The topics in this chapter include sugar amino acids, cyclo-
dextrins and carbohydrates as templates in the design of peptides and
proteins.
Chapter 6, ' De Novo Design of Proteins', by the editor, gives an over-
view of concepts in the design of proteins from general principles, rather
than through a redesign of natural structures. The focus is on structural
aspects, especially rules for the design of secondary structural elements
such as a-helical peptides, and the assembly of these into tertiary struc-
tures. Some de novo turn motifs, used to connect the secondary structural
elements, are also included. The chapter features an introduction to
foldamers, especially b- and g-peptides. It ends with examples of bio-
pharmaceutical applications of de novo design.
Chapter 7, 'Design of Insulin Variants for Improved Treatment of
Diabetes', by Thomas Hoeg-Jensen, provides a comprehensive overview
of the classical therapeutic peptide hormone insulin. The focus is on
insulin as a modern biopharmaceutical drug and the development
of new insulin variants with modulated therapeutic profiles, e.g.
prolonged-acting vs. fast-acting insulins, either by modifications in the