Structures and Solution Conformational Dynamics of Stylissamides G and H from the Bahamian Sponge Stylissa caribica

Abstract

Two new peptides, stylissamides G and H, were isolated from extracts of a sample of Stylissa caribica collected in deep waters of the Caribbean Sea. A single sample of S. caribica among a collection of 10 samples that were examined by LC-MS appeared to be a different chemotype from the others in that it lacked the familiar pyrrole-2-aminoimidazole alkaloids, stevensine and oroidin, and contained peptides of the stylissamide class. The structures of the title compounds were solved by integrated analysis of the MS and NMR spectra and chemical degradation. The solution conformation of stylissamide G was briefly examined by electronic circular dichroism and temperature-dependent 1H NMR chemical shifts of amide NH signals, which supported a conformationally rigid macrocycle.

Marine natural products

“…522 Plakilactone B, C, deshydroxyplakilactone B, 523 and des-hydroxygracilioether C 524 have been synthesised, 525 as has gracilioether E. 526,527 Peptides are common sponge metabolites and hence are targets of synthetic campaigns. Gombamide A, [528][529][530] stylissamide G, 531,532 and phakellistatin- 15 (ref. 533) were all synthesised in 2016, with the latter compound being inactive while the natural version inhibited the growth of several HTCLS, indicating the presence of a highly potent contaminant in the initial extract.…”

Composition and Predictive Functional Analysis of Bacterial Communities in Seawater, Sediment and Sponges in the Spermonde Archipelago, Indonesia

“…These compounds are of particular interest due, among other things, to their ability to inhibit protein kinases. Both Stylissa species, X. testudinaria and H. erectus, also produce a large range of highly selective antibiotic compounds [96][97][98][99].…”

New Tricks with an Old Sponge: Feature-Based Molecular Networking Led to Fast Identification of New Stylissamide L from Stylissa caribica

“…The absolute configuration of the seven amino acid residues was defined by an advanced Marfey's methodology, using the Orbitrap high-resolution MS instrument as detector to improve sensitivity and specificity and perform the analysis using only a few μg of sample [5,22]. Compound 1 (32 μg) was subjected to total hydrolysis by treating it with 6 N HCl/AcOH The NOESY spectrum of stylissamide L (1) showed many cross peaks between topologically far protons (e.g., Tyr-NH with Phe-NH or Tyr-NH with Pro I -H2; see also Table S2) suggesting a highly structured conformation as in other stylissamides [21]. The electronic circular dichroism (ECD) spectrum ( Figure S13) showed a quite complex band structure, with a positive Cotton effect at 236 nm and negative Cotton effects at 219 and 202 nm.…”

“…It has been shown that configurational isomerism about proline peptide bonds is possible in strained cyclic peptides like, for example, for stylissamide H and euryjanicin A [21]. Therefore, the cis or trans geometry of the bond of proline residues with the preceding amino acid should be considered a configuration rather than a conformation in such compounds, and needed to be clarified to complete structural elucidation of stylissamide L. Pro II was determined to be cis because of the NOESY cross peak between Pro II -H2 and Pro I -H2, and because The NOESY spectrum of stylissamide L (1) showed many cross peaks between topologically far protons (e.g., Tyr-NH with Phe-NH or Tyr-NH with Pro I -H2; see also Table S2) suggesting a highly structured conformation as in other stylissamides [21]. The electronic circular dichroism (ECD) spectrum ( Figure S13) showed a quite complex band structure, with a positive Cotton effect at 236 nm and negative Cotton effects at 219 and 202 nm.…”