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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.


CD spectra of PepK and PepE (upper panel) and CD analysis by CAPITO tool (lower panel) where both peptides are indicated as unfolded peptides.
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ijms-16-12159-f001: CD spectra of PepK and PepE (upper panel) and CD analysis by CAPITO tool (lower panel) where both peptides are indicated as unfolded peptides.

Mentions: The secondary structure of PepE and PepK in PBS was studied by circular dichroism (CD) spectroscopy and analyzed by the CAPITO web server (http://capito.nmr.fli-leibniz.de). As expected for very short peptide sequences, both peptides did not show any tendency to fold under this experimental condition [17]. CD spectra (Figure 1) show a typical shape of an unordered structure with a negative band between 197 and 201 nm. This behavior is also confirmed by CAPITO analysis [18], where spectra values—such as mean residue ellipticity (θ)—at λ = 200 nm are plotted versus λ = 222 nm. In fact, both the peptides are located in unfolded regions. It is important to notice that the CD spectrum of PepK presents also a maximum centered at 225 nm that has been already associated to the presence of fluctuating Polyproline II (PII) helices by various authors in recent papers [13,19,20].


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)

CD spectra of PepK and PepE (upper panel) and CD analysis by CAPITO tool (lower panel) where both peptides are indicated as unfolded peptides.
© Copyright Policy
Related In: Results  -  Collection

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

ijms-16-12159-f001: CD spectra of PepK and PepE (upper panel) and CD analysis by CAPITO tool (lower panel) where both peptides are indicated as unfolded peptides.
Mentions: The secondary structure of PepE and PepK in PBS was studied by circular dichroism (CD) spectroscopy and analyzed by the CAPITO web server (http://capito.nmr.fli-leibniz.de). As expected for very short peptide sequences, both peptides did not show any tendency to fold under this experimental condition [17]. CD spectra (Figure 1) show a typical shape of an unordered structure with a negative band between 197 and 201 nm. This behavior is also confirmed by CAPITO analysis [18], where spectra values—such as mean residue ellipticity (θ)—at λ = 200 nm are plotted versus λ = 222 nm. In fact, both the peptides are located in unfolded regions. It is important to notice that the CD spectrum of PepK presents also a maximum centered at 225 nm that has been already associated to the presence of fluctuating Polyproline II (PII) helices by various authors in recent papers [13,19,20].

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.