Design and Development of Peptides and Peptide Mimetics as Antagonists for Therapeutic Intervention

Abstract

The concept of peptides as therapeutic agents has been historically disregarded by the pharmaceutical industry on account of their susceptibility to degradation, their size and consequent limitations in methods of delivery. Recently, however, there has been a surge of interest in peptides and their mimetics as potential antagonists for therapeutic intervention. This is in part due to the increased half-life and oral availability that has been achieved for a number of peptide-based systems, the introduction and acceptance of alternative delivery methods, and the prevalence of proteomics to identify countless protein-protein interaction targets. The use of peptides and molecules that mimic their function therefore has great potential to effectively target a range of proteins that are pathogenically implicated in numerous diseases.

In silico study of peptide inhibitors against BACE 1

“…In future, chemical synthesis followed by in vitro and in vivo studies are required to establish the significance of this discovery. New technological developments in the field of peptidomics (Menschaert et al 2010;Mason 2010), peptidomimetics (Hruby and Cai 2013;Avan et al 2014) and drug design holds promise in modifying a primary peptide into a powerful inhibitor and subsequently to a peptide based drug.…”

Protein-Peptide Interactions Revolutionize Drug Development

“…Increase in the availability of crystallographic structures of protein complexes has conveyed valuable information for rational drug design efforts [36,37]. Given a known (or predicted) protein -protein complex structure, inhibitors that target the interface between the two proteins can interfere with this interaction.…”

“…Several rounds of screening might be necessary in order to isolate target specific binders. Finally, the tight binding peptides are identified by rapid sequence analysis [37,45]. Unlike rational design, screening phage displayed libraries for bioactive ligands requires no prior knowledge of the target structure [44].…”

“…There is significant discussion regarding the use of cell-penetrating peptides (CPPs) as tools to carry peptides to desired targets [37]. CPPs are usually 10-30 amino acids long and harbor a hydrophobic and a basic region.…”

Purity profiling of Peptide Drugs

“…Worldwide, more than 60 peptides are marketed, 270 are in clinicalphase testing and 400 in advanced preclinical phases. It is thus obvious that peptides show a great promise as drugs [1]. Although peptides demonstrate a high biological activity in combination with low toxicity and high specificity compared to small molecules, they suffer from low stability, low oral bioavailability and delivery issues [1][2][3][4].…”