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Two unprecedented natural Aib‐peptides with the (Xaa‐Yaa‐Aib‐Pro) motif and an unusual C‐terminus: structures, membrane‐modifying and antibacterial properties of pseudokonins KL III and KL VI from the fungus Trichoderma pseudokoningii
Author(s) -
Rebuffat Sylvie,
Goulard Christophe,
Hlimi Sanae,
Bodo Bernard
Publication year - 2000
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/1099-1387(200010)6:10<519::aid-psc273>3.0.co;2-6
Subject(s) - chemistry , motif (music) , combinatorial chemistry , structural motif , antibacterial peptide , antibacterial activity , stereochemistry , biochemistry , biology , bacteria , art , genetics , aesthetics
Abstract Pseudokonins KL III and KL VI are two natural ten‐residue peptides, which both contain the (Xaa‐Yaa‐Aib‐Pro) motif and exhibit an unusual C‐terminus. They have been isolated from the fungus Trichoderma pseudokoningii by intensive reversed‐phase HPLC, beside peptaibols classically C‐ended by a β‐amino alcohol. The amino acid sequences and the chemical structures of the C‐ends have been determined by the combined use of positive ion LSI‐MS and two‐dimensional homo‐ and heteronuclear NMR, including COSY, TOCSY, ROESY, 13 C heteronuclear single quantum correlation (HSQC) and heteronuclear multiple bond correlation (HMBC). Instead of one of the amino alcohols usually found as C‐terminal residue in peptaibols, pseudokonins KL III and KL VI are characterized by ‐Pro‐NH 2 and cyclo‐(Aib‐‐Proal) (Proal, prolinal), respectively. Such backbone modifications are described here for the first time for peptaibol antibiotics. The unusual cyclo‐(Aib‐‐Proal) C‐terminus is probably the result of an intramolecular cyclization of the two last Aib and Pro residues of a ten‐amino acid precursor, via a Proal intermediate. A secondary structure stabilized by –CO…H–N‐hydrogen bonds of the 1←4 type has been deduced for both peptides from ROESY data, 3 J NHC α Hcouplings and amide proton temperature coefficient values. The (Xaa‐Yaa‐Aib‐Pro) β‐bend ribbon spiral, which has been described for the first time in the case of a 14‐residue peptaibol containing three repetitive (Xaa‐Yaa‐Aib‐Pro) motifs (Ségalas G et al. Biopolymers 1999; 50: 71–85) appears to be maintained in the two shortened modified peptides. The β‐bend ribbon structure thus appears to be initiated by a single (Xaa‐Yaa‐Aib‐Pro) motif and unaffected by the C‐terminal modifications. However, the membrane and antibiotic properties of pseudokonins KL III and KL VI, point to the unfavourable effect of both shortening and cyclization of the peptide chain. Copyright © 2000 European Peptide Society and John Wiley & Sons, Ltd.