Solution structures of thiopeptide antibiotics

Abstract

A detailed NMR study of the thiopeptide amythiamicin D establishes its solution conformation and the presence of a single intramolecular hydrogen bond involving NH13 and O28, and also provides the first evidence for self-association of thiopeptides in solution.

NMR Structures of Thiostrepton Derivatives for Characterization of the Ribosomal Binding Site

“…These residues are in proximity to the nitrogen atoms of the adjacent thiazol(in)e ring, which could explain their high protection against exchange. In line with earlier reports, [12] we found atypical properties for the dehydroamino acids, which likely reflects their enamine character.…”

“…While 1 and related thiopeptides have been structurally characterized by NMR spectroscopy, [11] investigations on the conformation with current methods are scarce. [12] Here, we report solution-phase structures of 1 and three derivatives, and correlate their molecular interactions at the GAR of the 70S ribosome with their bioactivity.…”

NMR‐Strukturen von Thiostrepton‐Derivaten zur Charakterisierung der ribosomalen Bindetasche

“…Während 1 und verwandte Thiopeptide zur Strukturaufklärung früh durch NMR-Spektroskopie charakterisiert wurden, [11] sind Studien zur Konformation mit heute üblichen Methoden selten. [12] Wir berichten hier über die Strukturen von 1 sowie von drei Derivaten in Lösung und korrelieren ihre molekulare Wechselwirkung an der GAR des 70S-Ribosoms mit ihrer biologischen Aktivität.…”

“…Diese Reste liegen sehr nahe bei den Stickstoffatomen der benachbarten Thiazol(in)ringe, was ihre starke Abschirmung gegen chemischen Austausch erklären könnte. Über-einstimmend mit früheren Berichten [12] stellten wir untypische Eigenschaften der Dehydroaminosäuren fest, was wahrscheinlich an ihrem Enamincharakter liegt.…”

From Amino Acids to Heteroaromatics—Thiopeptide Antibiotics, Nature's Heterocyclic Peptides

“…Although our synthetic material appeared to be absolutely identical to the natural product, one signal in the 1 H NMR spectrum, assigned to NH29, showed significant concentration dependence. This prompted a more detailed NMR study [105] that not only revealed the presence of a single transannular hydrogen bond involving NH13 and O28, but also evidence for selfassociation of the thiopeptide in solution. These features are perhaps not surprising: with molecular weights of over 1000 Da, and arrays of rings linked by peptide bonds, the thiopeptides can be regarded as a microcosm of the protein world.…”