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Synthetic therapeutic peptides: science and market

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The decreasing number of approved drugs produced by the pharmaceutical industry, which has been accompanied by increasing expenses for R&D, demands alternative approaches to increase pharmaceutical R&D productivity. This situation has contributed to a revival of interest in peptides as potential drug candidates. New synthetic strategies for limiting metabolism and alternative routes of administration have emerged in recent years and resulted in a large number of peptide-based drugs that are now being marketed. This review reports on the unexpected and considerable number of peptides that are currently available as drugs and the chemical strategies that were used to bring them into the market. As demonstrated here, peptide-based drug discovery could be a serious option for addressing new therapeutic challenges.

Section snippets

Recent pharmaceutical market evolution

The pharmaceutical market is evolving in a context of increasing economic pressure. First, public authorities are pushing for lower healthcare costs through reduced drug pricing and increasing use of generic substitution. Second, regulatory authorities are more demanding in terms of drug efficacy, quality and safety, which – combined with (bio)technological progress – has led to an increase in pharmaceutical R&D costs [1]. At the beginning of the 2000s, the Tufts Center for the Study of Drug

Peptide limitations

Bioavailability and biodistribution of peptide drug candidates, which include absorption, transport, passage of biological membranes and cellular barriers, are determined by a combination of their physicochemical properties, such as aqueous solubility, lipophilicity, H-bond formation, chemical stability and metabolic stability (proteolytic and/or enzymatic degradation). With a few exceptions, peptides composed of natural amino acids are not very good drug candidates because of their intrinsic

Chemical strategies to improve peptide biological activity, specificity and stability

As discussed previously, the low bioavailability of peptides is due in part to high biodegradability by gastrointestinal, plasma and tissue peptidases. Moreover, their rapid removal from the circulation can also limit their therapeutic use. Absorption, distribution, metabolism and excretion processes play a pivotal part in defining the disposition of a drug candidate and, thus, its therapeutic effect [25]. To develop a peptide as a therapeutic agent, its biological effect, pharmacokinetic

Advantages of peptides over other drug candidates

Compared with proteins and antibodies, peptides have the potential to penetrate further into tissues owing to their smaller size. Moreover, therapeutic peptides, even synthetic ones, are generally less immunogenic than recombinant proteins and antibodies [35]. Peptides have other advantages over proteins and antibodies as drug candidates, including lower manufacturing costs (synthetic versus recombinant production), higher activity per unit mass (15–60-fold, assuming 75 kDa for one combining

Market for synthetic therapeutic peptides

The market for synthetic therapeutic peptides rose from €5.3 billion in 2003 to €8 billion in 2005. It has been estimated that it will reach €11.5 billion in 2013 [16]. This excludes peptides, proteins and antibodies extracted from natural sources or produced by recombinant DNA technology, cell-free expression systems, transgenic animals and plants and enzyme technology.

As described in Table 2, more than 60 synthetic therapeutic peptides (comprising those used for medical diagnostics or

Concluding remarks

As stated by Loffet [34], peptides (or proteins) still suffer from a deficit in image because they (generally) have to be injected, but erythropoietin and insulin are blockbusters even though they cannot be taken orally. We are convinced that chronic treatment with new formulations or routes of administration will give a new impetus to the therapeutic peptide field [52]. The majority of marketed peptide products and homologous compounds (proteins and antibodies) are peptide hormones or peptide

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