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Solution Structure of [Me‐ L ‐Leu 7 ]Didemnin B Determined by NMR Spectroscopy and Refined by MD Calculation
Author(s) -
Kessler Horst,
Mronga Siggi,
Will Martin,
Schmidt Ulrich
Publication year - 1990
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19900730104
Subject(s) - chemistry , conformational isomerism , heteronuclear molecule , moiety , nuclear magnetic resonance spectroscopy , side chain , crystallography , stereochemistry , ring (chemistry) , spectroscopy , molecule , organic chemistry , physics , quantum mechanics , polymer
Several homo‐ and heteronuclear two‐dimensional NMR techniques were used to assign all H‐ and C‐resonances of the two conformers A and B of [7‐( N ‐methyl‐ L ‐leucine)]didemnin B. Didemnine is a biologically highly active cytostaticum and immunosuppressivum. The assignment of the aliphatic C‐atoms were done by the inverse H,C‐COSY with TOCSY transfer which connects complete proton spin systems and represents them on C‐atoms. The structure of both conformers ( A and B ) in (D 6 )DMSO solution was derived from homo‐ and heteronuclear couplings ( J ), temperature dependencies of NH protons, and NOE effects. Distances determined from the latter were used for refinements by restrained MD calculations using the GROMOS program. The solution structure of [Me‐ L ‐Leu 7 ]didemnin B ( A and B ) was compared to that of didemnin B. The backbone structure of the macrocyclic ring and of the linear side‐chain moiety are very similar in conformer A and didemnin B , though the Ist 1 ‐Hip 2 region of the ring is slightly ex tended in conformer A . This may be caused by the influence of the Me‐ L ‐Leu 7 residue in A and may be responsible for its reduced biological activity in comparison to didemnin B . The more weakly populated conformer B exhibits a βVI turn in the linear side‐chain moiety.