Biomedical Engineering Reference
In-Depth Information
DIVERSITY-ORIENTED SYNTHESIS
OF AMINO ACID-DERIVED
SCAFFOLDS AND
PEPTIDOMIMETICS: A PERSPECTIVE
ANDREA TRABOCCHI
6.1
INTRODUCTION
Protein-protein interactions (PPIs) play a pivotal role in many biological mecha-
nisms, such as proteases complexation of substrates, the binding of peptide hor-
mones to receptors, and protein-protein interplay to produce signal transduction.
Nevertheless, the discovery of modulators of PPIs has been limited to structurally
characterized targets. As a consequence of interaction with their membrane-bound
receptors, bioactive peptides influence cell-cell communication and control a series
of vital functions, and a huge number of biologically active peptides have been discov-
ered and characterized, including hormones, vasoactive peptides, and neuropeptides.
Thus, they are of great interest in the biomedical field, and the number of native and
modified peptides used as therapeutics is ever increasing. Many bioactive peptides
have been prepared on a large scale and tested both in pharmacology and in the clinic,
thus allowing the development of new therapies for a variety of pathologies.
Nevertheless, the use of peptides as therapeutics is limited due to some factors,
including low metabolic stability toward proteolysis in the gastrointestinal tract, poor
absorption after oral ingestion, rapid excretion through liver and kidneys, and unde-
sired effects due to interaction of flexible peptides with several receptors [1]. More-
over, the conformational flexibility of most natural peptides and the high dependence
