Cyclic peptide unguisin A is an anion receptor with high affinity for phosphate and pyrophosphate

Abstract

Unguisin A (1) is a marine-derived, GABA-containing cyclic heptapeptide. The biological function of this flexible macrocycle is obscure. Here we show that compound 1 lacks any detectable activity in antimicrobial growth inhibition assays, a result that runs contrary to a previous report. However, we find that 1 functions as a promiscuous host molecule in a variety of anion-binding interactions, with high affinity particularly for phosphate and pyrophosphate. We also show that a series of rigidified, backbone-fluorinated analogues of 1 displays altered affinity for chloride ions.

Nidulantes of Aspergillus (Formerly Emericella): A Treasure Trove of Chemical Diversity and Biological Activities

“…The presence of GABA in (228-230) induces an enhanced conformational mobility relative to the cyclic peptides derived solely from R-amino acids. Such conformation-biological activity dependence strengthens the occurrence of GABA in 228-230 [114][115][116].…”

“…228 and 229 ( Figure 15) displayed moderate effects against Staphylococcus aureus, but no activity against Vibrio parahaemolyticus. Furthermore, the exogenous addition of L-leucine to the culture resulted in the production of unguisin D (231), which was detected by ion trap mass chromatography (LC-QIT-MS) [116]. Cyclic peptides are bio-synthesized through either ribosomal or nonribosomal mechanisms.…”

“…The presence of tryptophan derivatives (e.g., Emindoles) could lead to the discovery of an agent that improves cognition and reduces insomnia and depression. It is also noteworthy that nine peptides were reported as having Unguisin C (230) allowed the replacement of D-alanine with L-serine, leading to a peptide with more hydrophilicity, based on the oxidation of the methyl group in alanine to produce serine [116]. Unguisines 228-230 are the first naturally occurring compounds incorporating GABA in a cyclic peptide structure.…”

“…Structures of compounds 98-106.Emervaridione(105) and varioxiranediol(106) were published from E. variecolor (Figure 6)[70]. Koninginin H (107) (Figure 7), a polyketide derivative, was reported from E. nidulans, along with koninginin E and A (108 and 109), trichodermatide B (110), citrantifidiol(111), (4S,5R)-4-hydroxy-5-methylfuran-2-one (112), the glycerol derivatives gingerglycolipid B(113), (2S)-bis[9Z,12Z]-1-O,2-O-dilinoleoyl-3-O-[α-D-galactopyranosyl-(1"→6)β-D-galactopyranosyl] glycerol (114), (2S)-bis[9Z, 12Z]-1-O, 2-O-dilinoleoyl-3-O-β-Dgalactopyranosylglycerol(115) and cerebroside flavuside B(116), along with the known sterols β-sitosterol glucoside and ergosta-5,7,22-trien-3-ol[71]. Their antifungal effects were assessed towards Aspergillus (A.)…”

Marine natural products

“…279 The cyclic peptide unguisin A was shown to be a receptor for a range of anions, with highest affinity for phosphate and pyrophosphate. 280 The polyketide pallidopenillines were found to be growth stimulatory to a variety of grain crop seedlings 281 and ustusol A exhibited moderate activity against three species of plant pathogenic fungi. 282 Studies of the biosynthetic pathway to the indole diketopiperazine alkaloids echinulin and neoechinulin (originally isolated from various Aspergillus species), revealed that two prenyltransferases control a prenylation cascade in the biosynthesis and the second of these is able to accept its own polyprenylated derivatives as substrates and to catalyse prenylations at different sites.…”