Peptide Therapeutics and the Pharmaceutical Industry: Barriers Encountered Translating from the Laboratory to Patients

Abstract

Peptides are receiving increasing interest as clinical therapeutics. These highly tunable molecules can be tailored to achieve desirable biocompatibility and biodegradability with simultaneously selective and potent therapeutic effects. Despite challenges regarding up-scaling and licensing of peptide products, their vast clinical potential is reflected in the 60 plus peptide-based therapeutics already on the market, and the further 500 derivatives currently in developmental stages. Peptides are proving effective for a multitude of disease states including: type 2 diabetes (controlled using the licensed glucagon-like peptide-1 receptor liraglutide); irritable bowel syndrome managed with linaclotide (currently at approval stages); acromegaly (treated with octapeptide somatostatin analogues lanreotide and octreotide); selective or broad spectrum microbicidal agents such as the Gram-positive selective PTP-7 and antifungal heliomicin; anticancer agents including goserelin used as either adjuvant or monotherapy for prostate and breast cancer, and the first marketed peptide derived vaccine against prostate cancer, sipuleucel-T. Research is also focusing on improving the biostability of peptides. This is achieved through a number of mechanisms ranging from replacement of naturally occurring L-amino acid enantiomers with D-amino acid forms, lipidation, peptidomimetics, N-methylation, cyclization and exploitation of carrier systems. The development of self-assembling peptides are paving the way for sustained release peptide formulations and already two such licensed examples exist, lanreotide and octreotide. The versatility and tunability of peptide-based products is resulting in increased translation of peptide therapies, however significant challenges remain with regard to their wider implementation. This review highlights some of the notable peptide therapeutics discovered to date and the difficulties encountered by the pharmaceutical industry in translating these molecules to the clinical setting for patient benefit, providing some possible solutions to the most challenging barriers.

Self-assembling diphenylalanine peptide nanotubes selectively eradicate bacterial biofilm infection

“…Compared to carbon and metallic nanotubes, peptide variants possess the additional benefits of improved chemical versatility due to the range of amino acid functional groups, enhanced biocompatibility, tunable biodegradability and variable immunogenicity [17]. Interest in dipeptide nanotubes, for example the FF motif, is particularly high as the reduced amino acid chain length makes their synthesis and manufacturing upscale more cost-effective and amenable to widespread industrial applications [18]. Figure 1 (a-c) outlines the structure of the FF motifs studied, with (a) representing FF with a carboxylic acid terminus (NH2-FF-COOH), (b) corresponding the d-enantiomeric isomer of (a) (NH2-ff-COOH), and (c) FF possessing two amino terminals (NH2-FF-NH2).…”

Improved systemic delivery of insulin by condensed drug loading in a dimpled suppository

“…The novel highly functional peptide therapeutics, such as agents for cancer, diabetes mellitus, cardiovascular diseases, and rheumatoid arthritis, are clinically accessible and were found to have a favorable clinical effect (2)(3)(4). Although these peptides drastically improve the symptoms, their administration method is limited to injections, which lead to patient inconvenience due to pain, risks of infection, and the need for continuous ambulant use.…”

A Simple Platform for the Rapid Development of Antimicrobials

“…This allowed us to pre-stock large amounts of peptides for combinatorial production of the synbodies. Of note, the cost of synthesis of peptides has decreased notably and economies of scale enable the commercial production of numerous peptide therapeutics 25 . The second new feature was the development of a system for the rapid synthesis and screening of candidate synbodies.…”