Lipid membrane permeability of modified c[D‐Pen 2 , D‐pen 5 ]enkephalin peptides
1996; Wiley; Volume: 48; Issue: 1 Linguagem: Inglês
10.1111/j.1399-3011.1996.tb01110.x
ISSN0367-8377
AutoresVaradarajan Ramaswami, Xiaoyun Zhu, Marek Romanowski, RON C. HAASETH, Aleksandra Misicka, Andrzej W. Lipkowski, Victor J. Hruby, David F. O’Brien,
Tópico(s)Protein Structure and Dynamics
ResumoPermeability coefficients of a series of analogues of a potent opioid peptide, c[D‐Pen 2 , D‐Pen 5 ]enkephalin, were measured in a model membrane system. The analogues included hydrophobic amino acid substitutions on position 3. Liposomes of a mixed composition consisting of zwitterionic lipids and cholesterol served as the model membranes. The obtained permeability coefficients range between 0.38 × 10 −12 and 2.9 × l0 −12 cm/s. These data were correlated with the hydrophobicity scale of Nozaki and Tanford ( J. Biol. Chem. 246, 1971, 2211‐2217) (correlation coefficient = 0.9933) and with determinations of lipid order perturbation by differential scanning calorimetry (correlation coefficient = ‐0.9779). The reasonably good correlation obtained within the family of analogues substituted on position 3 (Gly, Ala, Leu, Phe) indicates that changes in permeabilities are primarily related to increases in the partition coefficient of the peptide. However, Phe residue added on the N ‐terminal end of the peptide (position 0) does not appear to follow the observed trend, showing stronger lipid perturbation and lower permeability compared to the Phe 3 analog. This observation demonstrates that each class of peptide modifications requires a new basis of permeability analysis and predictions. © Munksgaard 1996.
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