Transport of Model Peptides across Isolated Cuticle of Ascaris suum: Influence of Methylation and Hydrogen Bonds
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Authors
Sheehy, Barbara
Issue Date
1995
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
The goal of this study was to delineate the factors which
govern peptide transport across the cuticular/hypodermal complex
of the parasitic nematode, Ascaris suum. Data obtained from this
study are important to the successful development of peptidemimetic
antiparasitic drugs to combat infection of livestock,
thereby reducing parasite-related deaths and economic losses. We
hypothesized that the permeability properties of the nematode
cuticle would be similar to those obtained from previous studies
with human intestinal cell model systems. A series of structurally-related
model peptides was prepared from D-phenylalanine to study
the influence of hydrogen bonding on permeability across isolated
cuticle from A. suum. The amide nitrogens in the parent oligomer
were sequentially methylated to give a series containing varying
numbers of methyl groups. These peptides included AcfNH2, Acf(NMe-
f)2NH2, and Ac(N-Me-f)3NHMe. The permeability properties of
these peptides were studied using two-chamber diffusion cells and
radiolabeled peptides. Rates of transport across the isolated cuticle
for the three peptides were calculated from data collected from
liquid scintillation and HPLC techniques. The results of these
studies demonstrated a statistically significant increase in
permeability coefficients across the cuticle with the addition of
each methyl group. The peptide with three methyl groups and five
hydrogen bonds, Ac(N-Me-f)3NHMe, had an experimentally calculated
permeability coefficient of about 10-fold greater than the nonmethylated
peptide, AcfNH2, which contained five hydrogen bonds.
These results are in accordance with the hypothesis that a peptide
must possess both an affinity for the aqueous-membrane interface
and a reasonably low desolvation energy in order to efficiently
traverse the cuticular/hypodermal complex in nematodes.
Description
iv, 43 p.
Citation
Publisher
Kalamazoo College
License
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