Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Oct 26;14(11):194.
doi: 10.3390/md14110194.

Natural Proline-Rich Cyclopolypeptides from Marine Organisms: Chemistry, Synthetic Methodologies and Biological Status

Wan-Yin Fang  1 , Rajiv Dahiya  2 , Hua-Li Qin  3 , Rita Mourya  4 , Sandeep Maharaj  5
Affiliations
Review

Natural Proline-Rich Cyclopolypeptides from Marine Organisms: Chemistry, Synthetic Methodologies and Biological Status

Wan-Yin Fang et al. Mar Drugs. .

Abstract

Peptides have gained increased interest as therapeutics during recent years. More than 60 peptide drugs have reached the market for the benefit of patients and several hundreds of novel therapeutic peptides are in preclinical and clinical development. The key contributor to this success is the potent and specific, yet safe, mode of action of peptides. Among the wide range of biologically-active peptides, naturally-occurring marine-derived cyclopolypeptides exhibit a broad range of unusual and potent pharmacological activities. Because of their size and complexity, proline-rich cyclic peptides (PRCPs) occupy a crucial chemical space in drug discovery that may provide useful scaffolds for modulating more challenging biological targets, such as protein-protein interactions and allosteric binding sites. Diverse pharmacological activities of natural cyclic peptides from marine sponges, tunicates and cyanobacteria have encouraged efforts to develop cyclic peptides with well-known synthetic methods, including solid-phase and solution-phase techniques of peptide synthesis. The present review highlights the natural resources, unique structural features and the most relevant biological properties of proline-rich peptides of marine-origin, focusing on the potential therapeutic role that the PRCPs may play as a promising source of new peptide-based novel drugs.

Keywords: lipophilicity parameter; marine sponge; marine tunicate; peptide synthesis; pharmacological activity; proline-rich cyclic peptide; stereochemistry.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Proline-rich cyclic peptides (PRCPs) from marine sponges.
Figure 1
Figure 1
Proline-rich cyclic peptides (PRCPs) from marine sponges.
Figure 2
Figure 2
PRCPs from marine ascidians (tunicates) and cyanobacteria.
Figure 3
Figure 3
Modified amino acid moieties/heterocyclic rings present in marine-derived PRCPs.
Figure 4
Figure 4
The two possible conformations for the proline peptide bond.
Figure 5
Figure 5
Different conformers of cyclopolypeptide ceratospongamide.
Figure 6
Figure 6
General structures of l- and d-proline and their isomerization via proline racemase.
See this image and copyright information in PMC

References

    1. Bai R., Friedman S.J., Pettit G.R., Hamel E. Dolastatin 15, a potent antimitotic depsipeptide derived from Dolabella auricularia: Interaction with tubulin and effects on cellular microtubules. Biochem. Pharmacol. 1992;43:2637–2645. doi: 10.1016/0006-2952(92)90153-A. - DOI - PubMed
    1. Okamoto S., Iwasaki A., Ohno O., Suenaga K. Isolation and structure of kurahyne B and total synthesis of the kurahynes. J. Nat. Prod. 2015;78:2719–2725. doi: 10.1021/acs.jnatprod.5b00662. - DOI - PubMed
    1. Iwasaki A., Ohno O., Sumimoto S., Ogawa H., Nguyen K.A., Suenaga K. Jahanyne, an apoptosis-inducing lipopeptide from the marine cyanobacterium Lyngbya sp. Org. Lett. 2015;17:652–655. doi: 10.1021/ol5036722. - DOI - PubMed
    1. Jordan M.A., Walker D., de Arruda M., Barlozzari T., Panda D. Suppression of microtubule dynamics by binding of cemadotin to tubulin: Possible mechanism for its antitumor action. Biochemistry. 1998;37:17571–17578. doi: 10.1021/bi9817414. - DOI - PubMed
    1. Fusetani N., Warabi K., Nogata Y., Nakao Y., Matsunaga S., van Soest R.R.M. Koshikamide A1, a new cytotoxic linear peptide isolated from a marine sponge Theonella sp. Tetrahedron Lett. 1999;40:4687–4690. doi: 10.1016/S0040-4039(99)00844-8. - DOI

LinkOut - more resources