How structural features influence the biomembrane permeability of peptides

Journal of Pharmaceutical Sciences
P S BurtonR T Borchardt

Abstract

Successful drug development requires not only optimization of specific and potent pharmacological activity at the target site, but also efficient delivery to that site. Many promising new peptides with novel therapeutic potential for the treatment of AIDS, cardiovascular diseases, and CNS disorders have been identified, yet their clinical utility has been limited by delivery problems. Along with metabolism, a major factor contributing to the poor bioavailability of peptides is thought to be inefficient transport across cell membranes. At the present time, the reasons for this poor transport are poorly understood. To explore this problem, we have designed experiments focused on determining the relationship between peptide structure and peptide transport across various biological membranes both in vitro and in vivo. Briefly, peptides that varied systematically in chain length, lipophilicity, and amide bond number were prepared. Permeability results with these solutes support a model in which the principal determinant of peptide transport is the energy required to desolvate the polar amides in the peptide for the peptide to enter and diffuse across the cell membrane. Further impacting on peptide permeability is the presence of act...Continue Reading

References

Feb 1, 1976·Kidney International·S G Schultz
Apr 1, 1975·Journal of Pharmaceutical Sciences·R N SmithM M Ames
Dec 1, 1991·Pharmaceutical Research·R A ConradiP S Burton
Aug 1, 1990·Journal of Bioenergetics and Biomembranes·S E KaneM M Gottesman
Sep 1, 1990·Pharmaceutical Research·A R HilgersP S Burton
Apr 1, 1990·The Biochemical Journal·J E OdoomG F King
Sep 1, 1985·Brain Research Bulletin·W A Banks, A J Kastin
Dec 15, 1993·Biochemical and Biophysical Research Communications·P F AugustijnsD R Thakker
Sep 1, 1993·Pharmaceutical Research·A KimR H Guy
Feb 15, 1993·Biochemical and Biophysical Research Communications·P S BurtonN F Ho

❮ Previous
Next ❯

Citations

Mar 4, 2000·Journal of Controlled Release : Official Journal of the Controlled Release Society·W WangB Wang
Jun 6, 2000·Advanced Drug Delivery Reviews· T Borchardt RG M Pauletti
Sep 3, 2002·International Journal of Pharmaceutics·Nazila Salamat-MillerThomas P Johnston
Oct 18, 2000·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·B Testa, A J Bojarski
Oct 31, 1998·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·G CamenischG Folkers
Oct 31, 1998·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·G CamenischH van de Waterbeemd
Feb 28, 2001·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·F VeuillezP Buri
Nov 5, 2002·Bioorganic & Medicinal Chemistry·Changshou GaoKim D Janda
Dec 14, 2002·Journal of Molecular Graphics & Modelling·Susanne WiniwarterAnders Karlén
Sep 27, 2007·ACS Chemical Biology·Steven W MillwardRichard W Roberts
Jun 1, 2006·Journal of the American Chemical Society·Florian P Seebeck, Jack W Szostak
Oct 22, 2010·Journal of the American Chemical Society·John A McIntoshEric W Schmidt
Jun 26, 1999·The European Journal of Neuroscience·D S AlbeckA Granholm
Jul 1, 1997·The Journal of Pharmacy and Pharmacology·H Lennernäs
Oct 16, 1999·Journal of Controlled Release : Official Journal of the Controlled Release Society·R T Borchardt
Jul 16, 1999·The Journal of Peptide Research : Official Journal of the American Peptide Society·B WangR T Borchardt
Jul 16, 1999·The Journal of Peptide Research : Official Journal of the American Peptide Society·J T GoodwinP S Burton
Jul 16, 1999·The Journal of Peptide Research : Official Journal of the American Peptide Society·O S GudmundssonR T Borchardt
Jul 16, 1999·The Journal of Peptide Research : Official Journal of the American Peptide Society·O S GudmundssonR T Borchardt
Mar 13, 2014·Drug Development and Industrial Pharmacy·Javier O Morales, Jason T McConville
Nov 8, 2014·Artificial Cells, Nanomedicine, and Biotechnology·Kantrol Kumar SahuRavi Shankar Pandey
Oct 11, 2015·Journal of Pharmaceutical Sciences·Katharine Barbara SchowenMichael S Wolfe
Mar 29, 2002·Journal of Pharmaceutical Sciences·Peter T Mayer, Bradley D Anderson
Oct 3, 2003·Journal of Molecular Recognition : JMR·T LetohaB Penke
Dec 10, 2009·Peptides·Renata PerlikowskaAnna Janecka
Aug 4, 2009·Drug Discovery Today·Ahmad Reza Mehdipour, Mehrdad Hamidi
Apr 6, 2005·The Journal of Pharmacy and Pharmacology·M Kyle HaddenThomas A Dix
May 20, 2003·The Journal of Peptide Research : Official Journal of the American Peptide Society·V BoguslavskyA W Lipkowski
Feb 23, 2013·International Journal of Pharmaceutics·Jwala RenukuntlaAshim K Mitra

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Brain Barrier Regulation in Health & Disease

The blood brain barrier is essential in regulating the movement of molecules and substances in and out of the brain. Disruption to the blood brain barrier and changes in permeability allow pathogens and inflammatory molecules to cross the barrier and may play a part in the pathogenesis of neurodegenerative disorders. Here is the latest research in this field.

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.