– In the August 12 issue of the journal Nature, researchers
at the University of Pennsylvania detail the creation
of a library of small protein-like molecules that
can self-assemble to form hollow corkscrew-like pores
that could mimic pores seen in living systems. These
molecules, formed from short chains of amino acids
called peptides attached to tree-like fragments called
dendrons, represent the first successful attempt at
creating man-made pores that can form in solution
and in bulk.
variations on naturally-occurring and synthetic amino
acids, we could create a nearly unlimited variety
of pores of different shapes and sizes," said
Virgil Percec, a professor in Penn's Department of
Chemistry. "We can foresee creating pores to
mimic biological function, to filter out one molecule
from a solution or to carry specific molecules across
nature, proteins that form hollow pores are ubiquitous
to life, performing many essential tasks such as forming
channels to cross cell membranes, generating chemical
energy, guiding the shape of newly-made proteins and
even puncturing holes in the cell walls of bacteria.
application of the technology could, for example,
lead to better means of filtering drinking water from
seawater or to an entirely new class of antibiotics
by creating pores that poke holes in harmful bacteria,"
peptide subunit has arm-like projections that allow
it to bind to similar peptides in a spiraling fashion.
Held together by hydrogen bonds, the stable helix
created by these peptides forms in such a way as to
create a tube or channel, the width of which can be
modified by using different combinations of amino
found that the ability of the peptides to recognize
each other and self-assemble is sufficiently robust
to tolerate a wide range of modifications yet still
remain capable of forming pores," Percec said.
to the researchers, the self-assembling peptides can
form in and on the surface of microbial cell membranes,
a breakthrough with enormous therapeutic potential.
The ability to mimic the function of natural pores
has long been a goal made very difficult by the complex
chemistry of proteins. Indeed, life as we know it
would not exist if it were not for the membranes that
separate cells from the outside world. Likewise, cells
would not exist without the protein pores to cross
these membranes, importing substances necessary to
sustain the cell and exporting wastes or products
needed by other cells.
has come to our attention that, if we cannot precisely
recreate the structure of proteins found in nature,
then perhaps we can mimic their function and create
new biologically inspired systems that achieve the
same result," Percec said. "We can also
imagine a great many non-biological systems and chemical
processes that could benefit from a few good holes."
Funding for the research was provided by the National
Science Foundation and the Office of Naval Research.
researchers involved in the study include Andres E.
Dulcey, Venkatachalapathy S. K. Balagurusamy, Yoshiko
Miura, Jan Smidrkal, Mihai Petereca, Sami Nummelin
and Ulrica Edland of the Department of Chemistry;
Sergei A. Vinogradov of the Department of Biochemistry
and Biophysics; and Paul A. Heiney of the Department
of Physics and Astronomy.
University of Pennsylvania