Peptides And Peptide Conjugates: Therapeutics On The Upward Path

Abstract

The main benefit of natural peptides, peptide analogs and newly designed peptides as therapeutics, lies in their high selectivity and affinity, which are frequently in the nanomolar range. New drugs targeting protein-protein interactions often require larger interaction sites than small molecules can offer. Thus, many peptidic drugs are already applied in therapy at the current state. The next generation of peptide-based therapeutic agents is currently on its way from basic research to clinical studies and eventually to the pharmaceutical market. Development of more robust and long-lasting drugs owing to well-known and new stabilization strategies is yielding novel and continuously improving peptide drugs. The introduction of smart linkers that exhibit stability towards blood plasma but intracellular lability will lead to target-oriented activity, which might successfully decrease side effects. In this review, peptidic therapeutics on the market, in clinical studies and some of those in basic research are characterized. Stabilization strategies and intelligent linkers are discussed with respect to their use in peptide drug therapy.

Template-constrained macrocyclic peptides prepared from native, unprotected precursors

“…However, native peptides generally have poor pharmacological properties (20). Modifications that offset those limitations while stably recapitulating proteinbinding conformations are of considerable interest (14,(21)(22)(23).Ring-forming reactions are prominent among alterations found to improve the stability and performance of peptides (24-27). They find broad utility in synthesis and, increasingly, in combination with phage, ribosome, and mRNA display technologies (28-32).…”

“…Experimental data as well as computational/ bioinformatic efforts (9)(10)(11) to identify "short linear motifs" within signaling proteins suggest that the number of druggable PPIs has been underestimated (12,13). Considerable opportunity exists for new chemistry in this area (14). Synthetic peptides that target "hot spots" on protein surfaces are a logical entry to drug-discovery programs (15)(16)(17)(18)(19).…”

In silico study of peptide inhibitors against BACE 1

“…Even though high biodegradability, low bioavailability and low cellular uptake may be some of the limitations of peptide drugs, they can benefit from novel synthetic strategies for enhancing their drug-like properties (Pandey et al 2009;Vlieghe et al 2010). Currently, modifications that a prospective peptide drug candidate can undergo to enhance their efficacy include peptide stapling (Verdine and Hilinski 2012), backbone replacement (Fernández-Llamazares et al 2014), non-natural amino acid incorporation, pseudo peptide bonds, cyclization (Gentilucci et al 2010), conjugation (Gauthier and Klok 2008;Ahrens et al 2012) and so on.…”

Harnessing supramolecular peptide nanotechnology in biomedical applications

“…For instance, many peptides such as ecallantide and liraglutide have been utilized as therapeutics for the treatment of myriad human conditions. [7][8][9][10] As nanomedicines, these peptides exert their therapeutic functions as single molecules. However, there are also peptides that are known to exhibit therapeutic functions through self-assembled nanostructures.…”