Solution structures by NMR of a novel antifungal drug: Petriellin A.

@article{Dang2006SolutionSB,
  title={Solution structures by NMR of a novel antifungal drug: Petriellin A.},
  author={Jason W. Dang and Luigi Aurelio and Andrew B. Hughes and Robert T. C. Brownlee},
  journal={Organic \& biomolecular chemistry},
  year={2006},
  volume={4 20},
  pages={
          3802-7
        }
}
Petriellin A is a novel cyclic depsipeptide antifungal compound consisting of nine l-configured residues, one d-phenyllactic acid (PhLac) and three unknown chiral centres: two N-methyl-threonines (MeThr1 & MeThr2) and one N-methyl-isoleucine (MeIle). NMR experiments including 2D ROESY, NOESY along with structural and energy calculations predicted that the unknown chiral centres were all l-configured, which was later verified chemically. Simulated annealing, dynamics calculations and… 
3 Citations

Solution-Phase Peptide Synthesis; Synthesis of 'North-Western' and 'South-Eastern' Fragments of the Antifungal Cyclodepsipeptide Petriellin A

The solution-phase synthesis of two highly modified peptides, a hexamer and a heptamer, that constitute the two halves of the antifungal cyclic depsipeptide, Petriellin A, is reported.

Conformational properties of the residues connected by ester and methylated amide bonds: theoretical and solid state conformational studies

  • D. SiodłakAnna Janicki
  • Chemistry, Biology
    Journal of peptide science : an official publication of the European Peptide Society
  • 2010
A systematic theoretical analysis was performed on N‐acetyl‐L‐alanine N′‐methylamide and the analogues with the ester bond and selected structural modifications adopted primarily the conformation β, and described the structure‐activity relationship of the depsipeptides, limited by the structural complexity of these compounds.

References

SHOWING 1-10 OF 24 REFERENCES

Unique molecular conformation of aureobasidin A, a highly amide N-methylated cyclic depsipeptide with potent antifungal activity: X-ray crystal structure and molecular modeling studies.

This result explains the reason why four out of the seven amide bonds have to be methylated to manifest biological activity, i.e. the high N-methylation of aureobasidin is necessary to form only one well-defined conformation.

Three-dimensional structure of ectatomin from Ectatomma tuberculatum ant venom

Two-dimensional 1H NMR techniques were used to determine the spatial structure of ectatomin, a toxin from the venom of the ant Ectatomma tuberculatum, and structures were refined by unrestrained energy minimization using the CHARMm program.

Antifungals targeted to the cell wall.

Cell wall acting antifungals are inherently selective and fungicidal; two classes of compounds--nikkomycin Z targeted at chitin synthase, and echinocandin LY 303366 and pneumocand in L-743,872 targeted at alpha-1,3-glucan synthase--are currently in clinical development.

Effect of N-methyl substitution of the peptide bonds in luteinizing hormone-releasing hormone agonists.

For the first time, conversion of LHRH agonists to antagonists was observed as a result of N-methyl substitution in the peptide backbone, and the pharmacokinetics of all the analogues in the leuprolide series and of several others in the deslorelin and nafarelin series were determined.

Determination ofd-amino acids. I. Hydrolysis of DNP-l-amino acid methyl esters with carboxypeptidase-Y

Abstractl- andd-amino acids were treated with fluoroniditrobenzene to form DNP-derivatives. The latter were esterified with methanol in the presence of dry HCl gas to the corresponding methyl esters.

Macrocyclic peptidomimetics - Forcing peptides into bioactive conformations

A perspective review highlights examples of both natural and synthetic bioactive macrocyclic peptides containing constraints that fix conformation, and briefly illustrates the promise that receptor-based design holds for structural and functional mimicry of peptides by macrocycles.

C-terminal retroviral-type zinc finger domain from the HIV-1 nucleocapsid protein is structurally similar to the N-terminal zinc finger domain.

Two-dimensional NMR spectroscopic and computational methods were employed for the structure determination of an 18-residue peptide with the amino acid sequence of the C-terminal retroviral-type

Introduction to antifungal drugs.

  • W. Dismukes
  • Biology, Medicine
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
  • 2000
These lipid formulations offer several advantages over conventional amphotericin B, including increased daily dose of the parent drug (up to 10-fold), high tissue concentrations in the primary reticuloendothelial organs (lungs, liver, and spleen), decrease in infusion-associated side effects (especially liposomal amph esotericin B), and marked decrease in nephrotoxicity.

Design of a potent combined pseudopeptide endothelin-A/endothelin-B receptor antagonist, Ac-DBhg16-Leu-Asp-Ile-[NMe]Ile-Trp21 (PD 156252): examination of its pharmacokinetic and spectral properties.

N-methylation of Ile-20 resulted in a compound that retained full receptor affinity at both endothelin receptor subtypes along with enhanced proteolytic stability and cellular permeability and may be responsible for the observed enhanced metabolic stability.