Publication Date

2010

Document Type

Honors Thesis

Department

Biochemistry

Keywords

Gramicidins, Cyclic peptides, Bilayer lipid membranes, Ion channels, Dimers, Gramicidin A, Black lipid membranes, 23Na-NMR

Abstract

Cyclic peptides are ring structures that consist of alternating L-and D amino acids. In this thesis, CP 5-10 (six cyclic peptides synthesized by Dr. Juan R. Granja, University of Santiago, Spain, and colleagues) were shown to support Na+ flux in black lipid membranes (BLM) with conductances ranging from 33 to 667 pS. CPs ability to form active ion channels was confirmed with 23Na NMR. The previously proposed mechanism of cyclic peptide ion channel formation was that 6 to 10 flat CP rings stack on top of each other, perpendicular to the phospholipid bilayer (Hartgerink et al., 1995). However, CP-6 and CP-8 are strong dimers that can also function as ion channels as demonstrated in our BLM and 23Na NMR experiments. Therefore, we hypothesized that a dimer of the CPs associating across the membrane was sufficient to form an active ion channel. Our investigations were based on the concentration response of the membrane resistance in BLM. With this approach we were able to confirm the dimeric nature of Gramicidin A (a model ion channel). However, we were not able to evoke a concentration response of the CPs because of solubility difficulties. We were able to show that there was a suggestion of the dimeric nature of the CP ion channel formation because a CP-5 addition to both sides of the bilayer was needed in order to evoke single channel activity.

Language

English

Comments

105 p. : ill. (some col.) Honors Project-Smith College, Northampton, Mass., 2010. Includes bibliographical references (p. 102-105)

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