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    J Med Chem. 2008 Aug 28;51(16):4881-9. Epub 2008 Jul 31.

    Toward an optimal blood-brain barrier shuttle by synthesis and evaluation of peptide libraries.

    Malakoutikhah M, Teixidó M, Giralt E.

    Source

    Institut de Recerca Biomèdica (IRB Barcelona), Parc Científic de Barcelona, Baldiri Reixac 10, Barcelona, Spain.

    Abstract

    Several peptide families containing N-methylated amino acids were designed and synthesized using solid-phase peptide synthesis (SPPS). The permeability and phospholipophilicity of these compounds were studied by parallel artificial membrane permeability assay (PAMPA) and immobilized artificial membrane chromatography (IAMC) to select the best peptides in terms of length, terminal groups, and amino acid replacement to be used as carriers that pass through a model of the blood-brain barrier (BBB) by passive diffusion. Furthermore, the enzymatic stability of these peptides in human serum and their cell viability by MTT assay were tested. These peptide families showed great stability and nontoxicity. The three peptides that showed the greatest permeability were coupled to levodopa (a nonpassive permeating drug) and assessed. These peptides effectively transferred levodopa through an artificial membrane by means of passive diffusion.

    PMID:
    18666771
    [PubMed - indexed for MEDLINE]

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