Small Changes in the Primary Structure of Transportan 10 Alter the Thermodynamics and Kinetics of its Interaction with Phospholipid Vesicles Export

@article{citeulike:2371344, abstract = {Abstract: The kinetics and thermodynamics of binding of transportan 10 (tp10) and four of its variants to phospholipid vesicles, and the kinetics of peptide-induced dye efflux, were compared. Tp10 is a 21-residue, amphipathic, cationic, cell-penetrating peptide similar to helical antimicrobial peptides. The tp10 variants examined include amidated and free peptides, and replacements of tyrosine by tryptophan. Carboxy-terminal amidation or substitution of tryptophan for tyrosine enhance binding and activity. The Gibbs energies of peptide binding to membranes determined experimentally and calculated from the interfacial hydrophobicity scale are in good agreement. The Gibbs energy for insertion into the bilayer core was calculated using hydrophobicity scales of residue transfer from water to octanol and to the membrane/water interface. Peptide-induced efflux becomes faster as the Gibbs energies for binding and insertion of the tp10 variants decrease. If anionic lipids are included, binding and efflux rate increase, as expected because all tp10 variants are cationic and an electrostatic component is added. Whether the most important effect of peptide amidation is the change in charge or an enhancement of helical structure, however, still needs to be established. Nevertheless, it is clear that the changes in efflux rate reflect the differences in the thermodynamics of binding and insertion of the free and amidated peptide groups.}, address = {Department of Chemistry and Biochemistry, University of North Carolina Wilmington, Wilmington, North Carolina 28403}, author = {Yandek, Lindsay E. and Pokorny, Antje and Almeida, Paulo F.}, citeulike-article-id = {2371344}, citeulike-linkout-0 = {http://dx.doi.org/10.1021/bi702205r}, citeulike-linkout-1 = {http://pubs.acs.org/doi/abs/10.1021/bi702205r}, day = {9}, doi = {10.1021/bi702205r}, journal = {Biochemistry}, keywords = {membrane, peptide, thermodynamics, transportan}, month = {February}, posted-at = {2008-02-13 19:38:47}, priority = {2}, title = {Small Changes in the Primary Structure of Transportan 10 Alter the Thermodynamics and Kinetics of its Interaction with Phospholipid Vesicles}, url = {http://dx.doi.org/10.1021/bi702205r}, year = {2008} }

TY - JOUR ID - citeulike:2371344 L3 - citeulike-article-id:2371344 N2 - Abstract: The kinetics and thermodynamics of binding of transportan 10 (tp10) and four of its variants to phospholipid vesicles, and the kinetics of peptide-induced dye efflux, were compared. Tp10 is a 21-residue, amphipathic, cationic, cell-penetrating peptide similar to helical antimicrobial peptides. The tp10 variants examined include amidated and free peptides, and replacements of tyrosine by tryptophan. Carboxy-terminal amidation or substitution of tryptophan for tyrosine enhance binding and activity. The Gibbs energies of peptide binding to membranes determined experimentally and calculated from the interfacial hydrophobicity scale are in good agreement. The Gibbs energy for insertion into the bilayer core was calculated using hydrophobicity scales of residue transfer from water to octanol and to the membrane/water interface. Peptide-induced efflux becomes faster as the Gibbs energies for binding and insertion of the tp10 variants decrease. If anionic lipids are included, binding and efflux rate increase, as expected because all tp10 variants are cationic and an electrostatic component is added. Whether the most important effect of peptide amidation is the change in charge or an enhancement of helical structure, however, still needs to be established. Nevertheless, it is clear that the changes in efflux rate reflect the differences in the thermodynamics of binding and insertion of the free and amidated peptide groups. JF - Biochemistry AD - Department of Chemistry and Biochemistry, University of North Carolina Wilmington, Wilmington, North Carolina 28403 TI - Small Changes in the Primary Structure of Transportan 10 Alter the Thermodynamics and Kinetics of its Interaction with Phospholipid Vesicles KW - membrane KW - peptide KW - thermodynamics KW - transportan AU - Yandek, Lindsay AU - Pokorny, Antje AU - Almeida, Paulo PY - 2008/02/09/ UR - http://dx.doi.org/10.1021/bi702205r ER -