Roseabol A, a New Peptaibol from the Fungus Clonostachys rosea

Abstract

A new 11 amino acid linear peptide named roseabol A (1) and the known compound 13-oxo-trans-9,10-epoxy-11(E)-octadecenoic acid (2) were isolated from the fungus Clonostachys rosea. Combined NMR and MS analysis revealed that roseabol A (1) contained amino acid residues characteristic of the peptaibol family of peptides such as isovaline, α-aminoisobutyric acid, hydroxyproline, leucinol, and an N-terminal isovaleric acid moiety. The amino acid sequence was established by a combination of NMR studies and tandem MS fragmentation analyses, and the absolute configurations of the constituent amino acids of 1 were determined by the advanced Marfey’s method. Compound 2 showed inhibitory activity against Merkel cell carcinoma, a rare and difficult-to-treat type of skin cancer, with an IC50 value of 16.5 μM.

Cytotoxic Peptaibols from Trichoderma strigosum

“…Similarly, the NH of Aib at δ H 8.27 showed an HMBC correlation with the carbonyl of Val 3 as well as geminal methylbearing nonprotonated carbon at δ C 57.4, suggesting the linkage of Val 3 with Aib 4 . Then the Aib 4 was further connected with Ala 5 , Ile 6 , and Leuol 7 in a series based on the HMBC correlations of NH at δ H 8.02 of the Ala 5 with the carbonyl carbon of Aib 4 , NH at δ H 8.10 of Ile 6 with the carbonyl carbon of Ala 5 , and NH at δ H 7.71 of Leuol 7 with the carbonyl carbon of Ile 6 (Figure 2). As a result, the linear sequence of 1 was determined to be Oct-Gly 1 -Ala 2 -Val 3 -Aib 4 -Ala 5 -Ile 6 -Leuol 7 , which agreed with the results from ESIMS 2 .…”

Eleven‐Residue Peptaibols Isolated from Trichoderma longibrachiatum Rifai DMG‐3‐1‐1and Their Structure‐Activity Relationship

“…Combined analyses of 1 H-1 H COSY, HMBC, HSQC and TOCSY spectra further revealed the presence of 2 × Val, 2 × Leu, 2 × Pro, 2 × Aib, 1 × Asn, 1 × Ileol and N-Ac-Aib residues (Table 1), which were in accordance with the result of Marfey's analysis (Figure 3). The acetyl group was also assumed to be in one terminal as the cases found in known peptaibols, the HMBC of CO (δ C 170.8, Ac-)/NH-1 (δ H 8.59 s, Aib 1 ) indicated the first Aib 1 residue; subsequent ROESY correlations of NH-1/NH-2 (δ H 8.36 d, Asn 2 ), NH-2/NH-3 (δ H 7.70 d, Val 3 ), NH-3/NH-4 (δ H 7.34 d, Val 4 ), NH-4/NH-5(δ H 7.91 s, Aib 5 ), NH-5/δ-H 2 (δ H 3.64 -3.68 m, 3.39 dt, Pro 6 -δ-H 2 ), α-H (δ H 4.20 t, Pro 6 -α-H)/NH-7 (δ H 7.53 d, Leu 7 ), NH-7/ NH-8 (δ H 7.19 d, Leu 8 ), NH-8/NH-9(δ H 7.52 s, Aib 9 ), NH-9/δ-H 2 (δ H 3.62 -3.64 m, Pro 10 -δ-H 2 ) and α-H (δ H 4.22 -4.28 m, Pro 10 -α-H)/NH-11 (δ H 7.02 d, Ileol 11 ), established the planar structure of 6 as Ac-Aib 1 -Asn 2 -Val 3 -Val 4 -Aib 5 -Pro 6 -Leu 7 -Leu 8 -Aib 9 -Pro 10 -Ileol 11 , which was further confirmed by the MALDI-MS/MS analysis (Fig- ure 2) of 6.…”

“…Peptaibols are a family of linear peptides generally composed of 5-22 amino acid residues, characterized by N-acyl terminus, C-amino alcohol terminus, and a high proportion of nonproteinogenic amino acids such as αaminoisobutyric acid (Aib) or isovaline (Iva). [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] In the past five years, peptaibols have attracted attentions of many natural product researchers for their potential bioactivities including cytotoxicities, [1][2][3][4][6][7][8][9]11,15,16] antibacterial activities, [1,2,11,13] antifungal activities, [9,10,12] anti-plasmodial activities [5] and anti-viral activities, [14] et al Peptaibols have been isolated from several genera of fungus, such as Trichoderma, [2][3][4][8][9][10][12][13][14]…”

“…In the past five years, peptaibols have attracted attentions of many natural product researchers for their potential bioactivities including cytotoxicities, [1–4,6–9,11,15,16] antibacterial activities, [1,2,11,13] antifungal activities, [9,10,12] antiplasmodial activities [5] and anti‐viral activities, [14] et al. Peptaibols have been isolated from several genera of fungus, such as Trichoderma , [2–4,8–10,12–17] Acremonium , [1,7,11] and Clonostachys , [6] et al.…”

Rare Glutamic Acid Methyl Ester Peptaibols from Sepedonium ampullosporum Damon KSH 534 Exhibit Promising Antifungal and Anticancer Activity

“…The δ- methyl ester of glutamic acid is rarely recognized in natural peptaibols, with only five examples out of the over 1450 peptaibiotics reported in the literature so far [ 5 , 8 , 9 , 10 , 11 , 14 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 ]. The first occurrence was reported for four peptaibols named Trichorzianines (TA) 1896, TA1924, TA1910, and TA1924a isolated from Trichoderma atroviride by Panizel et al in 2013 [ 13 ].…”