Structural and biological aspects of natural bridged macrobicyclic peptides from marine resources

Abstract

Among peptide‐based drugs, naturally occurring bicyclic compounds have been established as molecules with unique therapeutic potential. The diverse pharmacological activities associated with bicyclic peptides from marine tunicates, sponges, and bacteria render them suitable to be employed as effective surrogate between complex and small therapeutic moieties. Bicyclic peptides possess greater conformational rigidity and higher metabolic stability as compared with linear and monocyclic peptides. The antibody‐like affinity and specificity of bicyclic peptides enable their binding to the challenging drug targets. Bridged macrobicyclic peptides from natural marine resources represent an underexplored class of molecules that provides promising platforms for drug development owing to their biocompatibility, similarity, and chemical diversity to proteins. The present review explores major marine‐derived bicyclic peptides including disulfide‐bridged, histidinotyrosine‐bridged, or histidinoalanine‐bridged macrobicyclic peptides along with their structural characteristics, synthesis, structure–activity relationship, and bioproperties.The comparison of these macrobicyclic congeners with linear/monocyclic peptides along with their therapeutic potential are also briefly discussed.

Bicyclic peptides: Paving the road for therapeutics of the future

“…Theonellamides and theopalauamides are histidinoalanine‐bridged bicyclic peptides from the marine sponge genus Theonella . [ 37 ] Theonellamide J and K (Figure 3c), as well as 5‐ cis ‐apoa‐theopalauamide, were recently discovered in Theonella swinhoei . [ 31 ] Similar to their structural relatives, [ 37 ] theonellamide J and K exhibited cytotoxic activity.…”

“…[ 37 ] Theonellamide J and K (Figure 3c), as well as 5‐ cis ‐apoa‐theopalauamide, were recently discovered in Theonella swinhoei . [ 31 ] Similar to their structural relatives, [ 37 ] theonellamide J and K exhibited cytotoxic activity. [ 31 ] In an effort to investigate their mechanism of action, the first identified histidinoalanine‐bridged bicycle theonellamide F [ 38 ] has been shown to bind membrane sterols and induce glucan overproduction.…”

Recent Updates on the Antimicrobial Compounds from Marine‐Derived Penicillium fungi

“…had inhibitory activities against a variety of bacteria and fungi. [88,89,90,91] These bacteria included E. coli, M. luteus, MRSA, P. aeruginosa and R. solanacearum. These fungi included A. alternate, B. cinerea, F. oxysporum, P. digitatum, and V. mali.…”

“…Other compounds derived from marine Penicillium spp. had inhibitory activities against a variety of bacteria and fungi [88,89,90,91] . These bacteria included E. coli , M. luteus , MRSA, P. aeruginosa and R. solanacearum .…”

Anti-Proliferative Potential of Secondary Metabolites from the Marine Sponge Theonella sp.: Moving from Correlation toward Causation

“…Marine sponges are rich sources for natural products and many compounds derived from these organisms have grabbed the attention of the scientific community since they possess complex structures that are difficult to elucidate and synthesize [1,2]. In 1969, cytarabine (Cytosar-U) became the first marine anti-cancer drug to be approved [3].…”