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Mollamides B and C, Cyclic hexapeptides from the indonesian tunicate Didemnum molle.

Donia MS, Wang B, Dunbar DC, Desai PV, Patny A, Avery M, Hamann MT - J. Nat. Prod. (2008)

Bottom Line: The structures were established using 1D and 2D NMR experiments.The relative configuration of mollamide B at the thiazoline moiety was determined using molecular modeling coupled with NMR-derived restraints.The new peptides have been evaluated for their antimicrobial, antimalarial, anticancer, anti-HIV-1, anti-Mtb, and anti-inflammatory activities.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacognosy, The University of Mississippi, USA.

ABSTRACT
Two new cyclic hexapeptides, mollamides B (1) and C (2), were isolated from the Indonesian tunicate Didemnum molle along with the known peptide keenamide A (3). The structures were established using 1D and 2D NMR experiments. The relative configuration of mollamide B at the thiazoline moiety was determined using molecular modeling coupled with NMR-derived restraints. Their absolute configuration was determined using Marfey's method. The new peptides have been evaluated for their antimicrobial, antimalarial, anticancer, anti-HIV-1, anti-Mtb, and anti-inflammatory activities. Keenamide A and mollamide B show cytotoxicity against several cancer cell lines.

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Energy-minimized conformations of MolB-R (1) and MolB-S (2).
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fig2: Energy-minimized conformations of MolB-R (1) and MolB-S (2).

Mentions: Due to the inherent limitations of experimental data to assign the absolute configuration of functional groups such as these, molecular modeling coupled with NMR-derived restraint information has exhibited significant potential for assigning relative and absolute configuration of many natural products and pharmaceutically relevant compounds.18–20 A similar approach has been used to assign the unknown configuration at the α-carbon of the thiazoline moiety of mollamide B. Molecular modeling was utilized to provide a reasonable prediction of configuration at the α-carbon of the thiazoline moiety based on conformational changes to the molecule associated with d- or l-configuration at this center. Using the ROESY data as distance restraints (Figure 1), molecular mechanics calculations involving stepwise minimization followed by restrained simulated annealing were performed to generate an ensemble of conformations for the two possible configurations at the α-carbon (d-Tzn (S): MolB-S; l-Tzn (R): MolB-R). Additionally, since molecular mechanics energies are empirical in nature, more accurate semiempirical quantum mechanical calculations were performed to calculate the heats of formation (ΔHf) for the lowest energy conformations. MolB-R appeared to be more stable than MolB-S by 8.5 kcal/mol. Also, MolB-R was found to be consistent with NMR-derived distance restraints, while MolB-S showed two significant violations (Figure 2). Thus, the configuration at the α-carbon of the thiazoline moiety was assigned to be R, corresponding to the l-amino acid configuration.


Mollamides B and C, Cyclic hexapeptides from the indonesian tunicate Didemnum molle.

Donia MS, Wang B, Dunbar DC, Desai PV, Patny A, Avery M, Hamann MT - J. Nat. Prod. (2008)

Energy-minimized conformations of MolB-R (1) and MolB-S (2).
© Copyright Policy - open-access - ccc-price
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2651694&req=5

fig2: Energy-minimized conformations of MolB-R (1) and MolB-S (2).
Mentions: Due to the inherent limitations of experimental data to assign the absolute configuration of functional groups such as these, molecular modeling coupled with NMR-derived restraint information has exhibited significant potential for assigning relative and absolute configuration of many natural products and pharmaceutically relevant compounds.18–20 A similar approach has been used to assign the unknown configuration at the α-carbon of the thiazoline moiety of mollamide B. Molecular modeling was utilized to provide a reasonable prediction of configuration at the α-carbon of the thiazoline moiety based on conformational changes to the molecule associated with d- or l-configuration at this center. Using the ROESY data as distance restraints (Figure 1), molecular mechanics calculations involving stepwise minimization followed by restrained simulated annealing were performed to generate an ensemble of conformations for the two possible configurations at the α-carbon (d-Tzn (S): MolB-S; l-Tzn (R): MolB-R). Additionally, since molecular mechanics energies are empirical in nature, more accurate semiempirical quantum mechanical calculations were performed to calculate the heats of formation (ΔHf) for the lowest energy conformations. MolB-R appeared to be more stable than MolB-S by 8.5 kcal/mol. Also, MolB-R was found to be consistent with NMR-derived distance restraints, while MolB-S showed two significant violations (Figure 2). Thus, the configuration at the α-carbon of the thiazoline moiety was assigned to be R, corresponding to the l-amino acid configuration.

Bottom Line: The structures were established using 1D and 2D NMR experiments.The relative configuration of mollamide B at the thiazoline moiety was determined using molecular modeling coupled with NMR-derived restraints.The new peptides have been evaluated for their antimicrobial, antimalarial, anticancer, anti-HIV-1, anti-Mtb, and anti-inflammatory activities.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacognosy, The University of Mississippi, USA.

ABSTRACT
Two new cyclic hexapeptides, mollamides B (1) and C (2), were isolated from the Indonesian tunicate Didemnum molle along with the known peptide keenamide A (3). The structures were established using 1D and 2D NMR experiments. The relative configuration of mollamide B at the thiazoline moiety was determined using molecular modeling coupled with NMR-derived restraints. Their absolute configuration was determined using Marfey's method. The new peptides have been evaluated for their antimicrobial, antimalarial, anticancer, anti-HIV-1, anti-Mtb, and anti-inflammatory activities. Keenamide A and mollamide B show cytotoxicity against several cancer cell lines.

Show MeSH
Related in: MedlinePlus