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  • Title: Influence of PEG length on conformational and binding properties of CCK peptides exposed by supramolecular aggregates.
    Author: Accardo A, Ringhieri P, Palumbo R, Morelli G.
    Journal: Biopolymers; 2014 Jul; 102(4):304-12. PubMed ID: 24752531.
    Abstract:
    Five novel peptide amphiphiles (PAs), with common formula (C18)2-PEGx-CCK8 in which the CCK8 peptide and the (C18)2-hydrophobic moiety are spaced by polyethylene linkers of different length (PEG moieties with molecular weights of 700, 1000, 1500, 2000, and 3000 Daltons) are described. They act as potential target-selective nanocarriers towards tumor cells overexpressing cholecistokynin receptors. PAs self-assemble in supramolecular aggregates, with hydrodynamic radius ranging between 63 and 104 nm, as indicated by DLS measurements. Fluorescence studies suggested that, irrespective from the PEG length, the tryptophan residue located at the center of the CCK8 sequence is completely surrounded by water molecules at high mobility. This result indicates a potential capability of all formulated nanovectors to recognize the overexpressed CCK-2 receptors. CD data suggest that CCK8 peptide, in most of PAs in their aggregate form, adopts a conformation allowing the interaction with the receptor. Anyway, biological data obtained by flow cytometry analysis indicate that the five PAs have a different binding ability towards the CCK-2 receptors, with higher binding properties shown by PA containing PEG with MW of 2000 Dalton. Therefore, PEG2000 can be considered as the best spacer in the formulation of nanovectors based on CCK8 peptide amphiphiles.
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