Toward tailor-made transmembrane ion channels: A designed peptide that folds into a unique βDL-helical species in solution

ORGN 384

Thomas D. Clark, thomas.clark@nrl.navy.mil1, Mallika Sastry, mallika_sastry@hms.harvard.edu2, and Gerhard Wagner, gerhard_wagner@hms.harvard.edu2. (1) Division of Chemistry, Naval Research Laboratory, 4555 Overlook Avenue SW, Washington, DC 20375, (2) Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115
This presentation describes the design and characterization of a synthetic peptide that folds into a well-defined, double-stranded bDL-helical species, as evidenced by solution NMR. bDL-helical peptides are interesting due to their ability to form transmembrane ion channels; the most well-known example is the natural peptide antibiotic gramicidin A. We are currently seeking to develop channel-forming peptides as alternatives to ion channel proteins for application in nanopore-based chemical and biological sensors. While channel-forming peptides offer potential advantages over ion channel proteins, including thermodynamic stability and ease of synthesis and functionalization, they also possess certain limitations, such as kinetic instability of the conductance state arising from fluctuations in conformation and/or degree of oligomerization. As a first step to overcoming these limitations, this presentation addresses the problem of designing a bDL-helical peptide having a well-defined conformation and oligomerization state.
 

Proteins, Peptides, Amino Acids, and Enzymes
8:00 AM-11:40 AM, Tuesday, 15 March 2005 Convention Center -- Room 9, Oral

Division of Organic Chemistry

The 229th ACS National Meeting, in San Diego, CA, March 13-17, 2005