The cyclic depsipeptide backbone of the didemnins.
An X-ray crystal analysis of phi-lactone N-¿1-¿N-¿4-¿[3- hydroxy-5-methyl-1-oxo-4-(N-L-threonylamino)heptyl]- oxy¿-2,5-dimethyl-1,3-dioxohexyl¿-L-leucyl¿-L-prolyl¿- N,O-dimethyl-L-tyrosine hydrobromide hydrate (1a), C42H66N5O11+.Br-.H2O, was obtained in order to determine the backbone folding of the macrocycle and to compare the results obtained with those reported previously for the natural product didemnin B (1b). Some differences were noted in the torsion angles of the two conformers of the hydrobromide salt, denoted (1a) and (1a'). The conformation of (1a') resembled the conformation of (1b) more closely than did that of (1a). Certain regions of both crystal backbones were more flexible than those in didemnin B; however, the transannular hydrogen bonds in both (1a) and (1a') were somewhat stronger than in (1b).
Department of Chemistry, University of Pennsylvania, Philadelphia 19104-6323, USA.
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Mayer
P J
PJ
Carroll
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MM
Joullié
D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000737:chemistry; D000998:Antiviral Agents / Q000737:chemistry; D018360:Crystallography, X-Ray; D047630:Depsipeptides; D006860:Hydrogen Bonding; D007166:Immunosuppressive Agents / Q000737:chemistry; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000737:chemistry*; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D047630:Depsipeptides; D007166:Immunosuppressive Agents; D010456:Peptides, Cyclic; C030051:didemnins