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Conformational ensembles explored dynamically from disordered peptides targeting chemokine receptor CXCR4.

Vincenzi M, Costantini S, Scala S, Tesauro D, Accardo A, Leone M, Colonna G, Guillon J, Portella L, Trotta AM, Ronga L, Rossi F - Int J Mol Sci (2015)

Bottom Line: These results were further confirmed by MD simulations that demonstrated the ability of the peptides to assume conformational ensembles.They revealed a network of transient and dynamic H-bonds and interactions with water molecules.Moreover, our data indicate that these peptides represent useful tools for molecular recognition processes in which a flexible conformation is required in order to obtain an interaction with a specific target.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy University of Naples "Federico II", and CIRPeB, Via Mezzocannone 16, I-80134 Naples, Italy. marian.vincenzi@unina.it.

ABSTRACT
This work reports on the design and the synthesis of two short linear peptides both containing a few amino acids with disorder propensity and an allylic ester group at the C-terminal end. Their structural properties were firstly analyzed by means of experimental techniques in solution such as CD and NMR methods that highlighted peptide flexibility. These results were further confirmed by MD simulations that demonstrated the ability of the peptides to assume conformational ensembles. They revealed a network of transient and dynamic H-bonds and interactions with water molecules. Binding assays with a well-known drug-target, i.e., the CXCR4 receptor, were also carried out in an attempt to verify their biological function and the possibility to use the assays to develop new specific targets for CXCR4. Moreover, our data indicate that these peptides represent useful tools for molecular recognition processes in which a flexible conformation is required in order to obtain an interaction with a specific target.

No MeSH data available.


Comparison of 2D [1H, 1H] TOCSY (left) and ROESY (right) spectra of PepE in H2O/D2O (90/10). The HN-aliphatic protons correlation regions are shown in each panel; spin system assignments are indicated in the left side. In the right panel, sequential ROE contacts are highlighted by rectangles and the corresponding assignments are indicated.
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ijms-16-12159-f002: Comparison of 2D [1H, 1H] TOCSY (left) and ROESY (right) spectra of PepE in H2O/D2O (90/10). The HN-aliphatic protons correlation regions are shown in each panel; spin system assignments are indicated in the left side. In the right panel, sequential ROE contacts are highlighted by rectangles and the corresponding assignments are indicated.

Mentions: In aqueous solution, the poor spectral dispersion of the 1D [1H] spectra and the almost complete absence of signal in the 2D [1H, 1H] NOESY [21] experiments indicated that both peptides were very flexible (data not shown). However, complete proton resonance assignments were achieved by combined analysis of the 2D [1H, 1H] TOCSY [22] and ROESY [23] spectra (Figure 2 and Figure 3; Tables S1 and S2).


Conformational ensembles explored dynamically from disordered peptides targeting chemokine receptor CXCR4.

Vincenzi M, Costantini S, Scala S, Tesauro D, Accardo A, Leone M, Colonna G, Guillon J, Portella L, Trotta AM, Ronga L, Rossi F - Int J Mol Sci (2015)

Comparison of 2D [1H, 1H] TOCSY (left) and ROESY (right) spectra of PepE in H2O/D2O (90/10). The HN-aliphatic protons correlation regions are shown in each panel; spin system assignments are indicated in the left side. In the right panel, sequential ROE contacts are highlighted by rectangles and the corresponding assignments are indicated.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4490436&req=5

ijms-16-12159-f002: Comparison of 2D [1H, 1H] TOCSY (left) and ROESY (right) spectra of PepE in H2O/D2O (90/10). The HN-aliphatic protons correlation regions are shown in each panel; spin system assignments are indicated in the left side. In the right panel, sequential ROE contacts are highlighted by rectangles and the corresponding assignments are indicated.
Mentions: In aqueous solution, the poor spectral dispersion of the 1D [1H] spectra and the almost complete absence of signal in the 2D [1H, 1H] NOESY [21] experiments indicated that both peptides were very flexible (data not shown). However, complete proton resonance assignments were achieved by combined analysis of the 2D [1H, 1H] TOCSY [22] and ROESY [23] spectra (Figure 2 and Figure 3; Tables S1 and S2).

Bottom Line: These results were further confirmed by MD simulations that demonstrated the ability of the peptides to assume conformational ensembles.They revealed a network of transient and dynamic H-bonds and interactions with water molecules.Moreover, our data indicate that these peptides represent useful tools for molecular recognition processes in which a flexible conformation is required in order to obtain an interaction with a specific target.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy University of Naples "Federico II", and CIRPeB, Via Mezzocannone 16, I-80134 Naples, Italy. marian.vincenzi@unina.it.

ABSTRACT
This work reports on the design and the synthesis of two short linear peptides both containing a few amino acids with disorder propensity and an allylic ester group at the C-terminal end. Their structural properties were firstly analyzed by means of experimental techniques in solution such as CD and NMR methods that highlighted peptide flexibility. These results were further confirmed by MD simulations that demonstrated the ability of the peptides to assume conformational ensembles. They revealed a network of transient and dynamic H-bonds and interactions with water molecules. Binding assays with a well-known drug-target, i.e., the CXCR4 receptor, were also carried out in an attempt to verify their biological function and the possibility to use the assays to develop new specific targets for CXCR4. Moreover, our data indicate that these peptides represent useful tools for molecular recognition processes in which a flexible conformation is required in order to obtain an interaction with a specific target.

No MeSH data available.