Structure of a new cyclotetrapeptide trapoxin A

Nakai, Hiroshi; Nagashima, K.; Itazaki, Hiroshi

doi:10.1107/s0108270190012987

Cited by 15 publications

(17 citation statements)

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“…All conformers of the five macrocycles 7a, 7b, 7e, 7f, and 7h showed a cis-conformation between the nitrogen atom of their respective D-prolyl residue and the amide carbon of the adjacent amino acid (ωC). The trans-trans-cis-trans sequence of the backbone has also been reported for the model structure apicidin (1) [69] and similar cyclotetrapeptides [78]. The largest deviations from the ideal dihedral angle were measured between the nitrogen atoms of the large aromatic side chains Lphenylalanine or L-tryptophan and the amide carbon of the following building blocks (ωA).…”

Section: Multiconformational Equilibrium Detected By Nmrsupporting

confidence: 53%

Macrocyclic Tetramers – Structural Investigation of Peptide-Peptoid Hybrids

Herlan¹,

Sonnefeld²,

Glöge³

et al. 2021

Preprint

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The determination of the three-dimensional structure is a key step for the identification of new targets as well as the rational design of bioactive compounds. Herein, we report the synthesis and the structural elucidation of novel tetrameric macrocycles. Measurements were taken in solid and solution states with the help of X-ray scattering and NMR spectroscopy. The investigations made will help to find diverse applications for this new, promising compound class.

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Section: Multiconformational Equilibrium Detected By Nmrsupporting

confidence: 53%

Macrocyclic Tetramers – Structural Investigation of Peptide-Peptoid Hybrids

Herlan¹,

Sonnefeld²,

Glöge³

et al. 2021

Preprint

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“…High‐resolution three‐dimensional structures of these cyclic natural products have been reported for romidepsin ( 5 , X‐ray and NMR), trapoxin A ( 12 a , X‐ray), chlamydocin ( 13 a , NMR), WF‐3161 ( 15 , NMR), HC‐toxin ( 16 , NMR), FR235222 ( 18 , NMR), apicidin ( 24 a , X‐ray and NMR), azumamide A ( 25 a , NMR), and azumamide E ( 25 e , NMR) . The structural data reveal that the backbones of the macrocyclic structures can adapt different conformations depending on the solvent.…”

Section: Structural Insight Into Macrocyclic Hdac Inhibitorsmentioning

confidence: 99%

Natural and Synthetic Macrocyclic Inhibitors of the Histone Deacetylase Enzymes

et al. 2016

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Inhibition of histone deacetylase (HDAC) enzymes has emerged as a target for development of cancer chemotherapy. Four compounds have gained approval for clinical use by the Food and Drug Administration in the US, and several are currently in clinical trials. However, none of these compounds possesses particularly good isozyme selectivity, which would be a highly desirable feature in a tool compound. Whether selective inhibition of individual HDAC isozymes will provide improved drug candidates remains to be seen. Nevertheless, it has been speculated that using macrocyclic compounds to target HDAC enzymes might hold an advantage over the use of traditional hydroxamic‐acid‐containing inhibitors, which rely on chelation to the conserved active‐site zinc ion. Here we review the literature on macrocyclic HDAC inhibitors obtained from natural sources and on structure–activity relationship studies inspired by these molecules, as well as on efforts aimed at fully synthetic macrocyclic HDAC inhibitors.

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“…In fact cyclotetrapeptides in general are rather scarce in the literature. This is not too surprising since these 12-membered rings are very strained as can be inferred from the fact that most of them crystallize with either 25 % [67] or even 50 % [68][69][70][71][72][73][74][75][76] of their amide bonds in a more energetic cis conformation. It is therefore amazing that macrolactam 1 crystallizes from MeOH solution in a C 2 conformation corresponding to a cyclotetrapeptide with four trans amides ( Figure 9a).…”

Section: Structures Of Supramolecular Assembliesmentioning

confidence: 99%

Efficient Synthesis and Astonishing Supramolecular Architectures of Several Symmetric Macrolactams

Baillargeon

Bernard

Gauthier

et al. 2007

Chemistry A European J

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The synthesis of four C(n) symmetric macrocyclic lactams cyclo-[NH-CH(2)-CH=CH-CH(2)-CO](n) (1, n=2; 2, n=3; 3, n=4) and cyclo-[NH-CH(2)-CH(2)-CH=CH-CO](3) (4) has been achieved by two approaches. A linear route leads to precursors that are subsequently macrocyclized in a separate step. The second, convergent approach relies on the symmetry of the targets: it includes suitably activated subunits, which are subjected to macrocyclization conditions. The subunits first oligomerize, then cyclize to form either pure macrolactams or mixtures. The macrolactam units 1, 2 and 4 stack on top each other through weak interactions (hydrogen bond and van der Waals), to form endless square, rectangular and triangular prisms, respectively. These stacks are further packed side by side in crystals grown from isotropic media. The overall dipoles in the crystals from lactams 1 and 4, which result mostly from the alignment of amide groups, are zero and large, respectively. Macrolactam 2 displays an astonishing isomorphism when allowed to cool down in anisotropic liquid crystal solutions. Large hollow hexagonal tubes are then obtained through a fractal process. Contrary to the three previous rings, 3 yields crystals where prisms of any shape are absent.

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Structure of a new cyclotetrapeptide trapoxin A

Cited by 15 publications

References 0 publications

Macrocyclic Tetramers – Structural Investigation of Peptide-Peptoid Hybrids

Macrocyclic Tetramers – Structural Investigation of Peptide-Peptoid Hybrids

Natural and Synthetic Macrocyclic Inhibitors of the Histone Deacetylase Enzymes

Efficient Synthesis and Astonishing Supramolecular Architectures of Several Symmetric Macrolactams

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