Complete 1H and 13C NMR assignments of tallysomycin s10b by modern two-dimensional NMR techniques

✍ Scribed by Catherine P. Freyder; Luigi G. Marzilli

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 980 KB
• Volume: 29
• Category: Article
• ISSN: 0749-1581
• DOI: 10.1002/mrc.1260290410

✦ Synopsis

Abstract

The ^1^H and ^13^C NMR spectra of tallysomycin s~10b~ (TLM), a third‐generation analog of bleomycin, were completely assigned through the use of two‐dimensional NMR experiments (NOESY, HOHAHA, HMQC, HMBC) in D~2~O at pH 2.5 and 6.8 (uncorrected values). Significant differences in the resonances for the β‐aminoalanine, β‐hydroxyhistidine and pyrimidinylpropionamide residues were observed owing to the protonation/deprotonation of these moieties. The assignments for TLM at pH 6.8 were compared with the latest 2D NMR‐based assignments of bleomycin A~2~ (BLM A~2~) at pH 6.7. In general the agreement was excellent, in view of the size and complexity of these anticancer antibiotics. Of the several differences found, most can be attributed to the different substitution patterns in the variable regions of the larger TLM and the BLM A~2~. Both drugs have similar structures in the region of protonation. For this invariant region of the molecules, comparison of the TLM ^13^C data at pH 2.5 with the 1D BLM A~2~ ^13^C data at low pH revealed that protonation induced similar changes in chemical shift for the corresponding signals in the two drugs. It is particularly noteworthy that the glucose and mannose ^13^C signals shift in a very similar manner for both drugs. Since the protonation shifts of the signals of these two sugars are much too large to be attributed to inductive effects, it is highly likely that both drugs, despite the structural differences in the variable region, undergo the same conformationl changes of the gulose and mannose moieties. These chemical shift similarities at both low and high pH confirm the validity of the assignments made independently on these two large drug molecules. The few differences between the two most recent ^13^C assignments of BLM A~2~, which are based on modern 2D NMR methods, can be resolved using the TLM assignments.