Peptides, Peptidomimetics, and Polypeptides from Marine Sources: A Wealth of Natural Sources for Pharmaceutical Applications

Abstract

Nature provides a variety of peptides that are expressed in most living species. Evolutionary pressure and natural selection have created and optimized these peptides to bind to receptors with high affinity. Hence, natural resources provide an abundant chemical space to be explored in peptide-based drug discovery. Marine peptides can be extracted by simple solvent extraction techniques. The advancement of analytical techniques has made it possible to obtain pure peptides from natural resources. Extracted peptides have been evaluated as possible therapeutic agents for a wide range of diseases, including antibacterial, antifungal, antidiabetic and anticancer activity as well as cardiovascular and neurotoxin activity. Although marine resources provide thousands of possible peptides, only a few peptides derived from marine sources have reached the pharmaceutical market. This review focuses on some of the peptides derived from marine sources in the past ten years and gives a brief review of those that are currently in clinical trials or on the market.

Keywords: antifungal peptides; antimicrobial peptides; extraction of peptides; marine peptides.

Figure 1

A schematic representation of the general extraction procedure for marine peptides. * Stages where bioassays are performed for screening.

Figure 2

A schematic representation of the solvent gradient extraction procedure of different components from natural marine sources. Adapted from Riguera, R. J. Mar. Biotechnol. 1997, 5, 187–193.

Figure 3

Classification of marine sources of peptides/peptidomimetics and their possible therapeutic applications.

Figure 4

Callyaerin, a cyclic peptide derived from Indonesian sponge. Adapted and reproduced with permission from Elsevier, Ibrahim et al. Bioorg. Med. Chem. 2010, 18, 4947–4956.

Figure 5

Peptides derived from the marine sponge Discodermia calyx. Reprinted with permission from Kimura et al. J. Nat. Prod. 2012, 75, 290–294. Copyright (2012) American Chemical Society.

Figure 6

Antifungal and cytotoxic bicyclic dodecapeptides obtained from a marine sponge of Theonella species. Adapted from Youssef et al. Mar. Drugs 2014, 12, 1911–1923. Reprinted with permission from Matsunaga et al. J. Org. Chem. 1995, 60, 1177–1181. Copyright (1995) American Chemical Society.

Figure 7

Pipecolidepsins A and B; cyclic depsipeptides identified from the extraction of the Madagascan Sponge Homophymia lamellose. Reprinted with permission from Coello et al. J. Nat. Prod. 2014, 77, 298–303. Copyright (2014) American Chemical Society.

Figure 8

Cyclic depsipeptides known as didemnins identified from the extraction of the Caribbean tunicate Trididemnum solidum. Reprinted with permission from Xu et al. J. Am. Chem. Soc. 2012, 134, 8625–8632. Copyright (2012) American Chemical Society.

Figure 9

Peptidomimetics terrelumamides A (1) and B (2) isolated from the marine fungus Aspergillus terreus. Adapted from You et al. Mar. Drugs 2015, 13, 1290–1303.

Figure 10

Structure of brentuximab vedotin. Adapted and reproduced with permission from Peter D Senter, Eric L Sievers. Nat. Biotechnol. 2012, 30, 631–637. Copyright (2012) Nature Publishing Group. mAb, monoclonal antibody; Val-Cit, Valine-Citrulline (linker); PABC, p-aminobenzyloxycarbonyl (spacer); MMAE, Monomethylauristatin E (a synthetic antineoplastic agent).

Figure 11

Derivative of didemnin known as Aplidine (Plitidepsin). Reprinted with permission from Adrio et al. J. Org. Chem. 2007, 72, 5129–5138. Copyright (2007) American Chemical Society.