Mark P. Foster

Biomedical Potential of Marine Natural Products

Marine natural products, the secondary or nonprimary metabolites produced by organisms that live in the sea, have received increasing attention from chemists and pharmacologists during the last two decades. Interest on the part of chemists has been twofold: natural products chemists have probed marine organisms as sources of new and unusual organic molecules, while synthetic chemists have followed by targeting these novel structures for development of new analogs and new synthetic methodologies and strategies (Albizati et al., 1990). The rationale for investigating the chemistry of marine organisms has changed over the past several decades. Early investigations were largely of a “phytochemical” nature, reporting detailed metabolite profiles similar to those reported for terrestrial plants in previous decades. However, analogous to investigations of terrestrial plants, more recent studies of marine organisms have focused on their potential applications, particularly to the treatment of human disease and control of agricultural pests (Fautin, 1988). Pharmacological evaluations of marine natural products have likewise undergone an evolution over the past two decades: beginning with the early investigations of toxins, followed by studies of cytotoxic and antitumor activity, to the present day, where a myriad of activities based on whole-animal models and receptor-binding assays are being pursued. The intent of this chapter is to look back at the evolution of biomedically oriented natural product studies of marine organisms, to chronicle the key developments, discoveries, and advances in the level of sophistication that have fueled further interest in this field, and finally to look forward at the future biomedical potential of marine natural products.

Natural Product Peptides from Marine Organisms

This chapter reviews the literature on peptides and modified peptides isolated from marine animals and plants that appear to be products of secondary metabolic pathways (i.e., do not appear to have a primary metabolic function). Although the focus is towards biologically active peptides, marine peptides with unique stuctures are also discussed, regardless of whether they have reported biological activity. Polypeptides, e.g., enzymes, structural proteins and receptor molecules will be specifically excluded from this discussion, as they are more appropriate for a biochemistry review article. For the purpose of this review, peptides will be defined as compounds derived biosynthetically from the condensation of at least two amino acids to produce a peptide (amide) bond, which may or may not have undergone further modification.

Nairaiamides A and B. two novel di-proline heptapeptides isolated from a fijian Lissoclinum bistratum ascidian.

Two new cyclic heptapeptides (1, 2) have been isolated from the ascidian Lissoclinum bistratum, and their structures determined by a combination of spectroscopic techniques, including a natural abundance two-dimensional 1H{13C,1H}-HMQC-TOCSY experiment which was pivotal to assigning and identifying the amino acid residues. 1H({13C}-HMBC and [1H-1H]-ROESY experiments provided the correlations necessary to sequence the peptides. In both peptides, the Ile-Pro amide bonds adopt cis configurations.