Stellettapeptins A and B, HIV-inhibitory cyclic depsipeptides from the marine sponge Stelletta sp

Abstract

Two new HIV-inhibitory depsipeptides, stellettapeptins A (1) and B (2), were isolated from an extract of the marine sponge Stelletta sp., collected from northwestern Australia. Structures of these cyclic nonribosomal peptides were elucidated on the basis of extensive NMR data analysis, and chemical degradation and derivatization studies. Stellettapeptins contain numerous nonproteinogenic amino acid residues and they are the first peptides reported to contain a 3-hydroxy-6,8-dimethylnon-4-(Z)-enoic acid moiety. Compounds 1 and 2 potently inhibit infection of human T-lymphoblastoid cells by HIV-1_RF with EC₅₀ values of 23 and 27 nM, respectively.

Keywords: Anti-HIV; Depsipeptide; Sponge peptide; Stelletta.

Figure 1

Structures and composition of stellettapeptins A (1) and B (2).

Figure 2

Key HMBC, ROESY, and COSY correlations for 1.

Figure 3

Anti-HIV activity of compounds 1 and 2. Uninfected cell cultures reveal direct cytotoxicity of the test samples. HIV infected cultures show cytoprotective effects of 1 and 2 against viral infection at lower concentrations, and cytotoxic effects at higher concentrations.