Samuel H. Gellman talks with
ScienceWatch.com and answers a few questions about
this month's New Hot Paper in the field of Chemistry.
Photo credit: Dan Yang.
Article Title: Foldamers with Heterogeneous
Backbones Authors: Horne,
Journal: ACCOUNT CHEM RES
Year: OCT 2008
* Univ Wisconsin, Dept Chem, 1101 Univ Ave, Madison, WI 53706
* Univ Wisconsin, Dept Chem, Madison, WI 53706 USA.
Why do you think your paper is highly
Broad attention to this paper reflects increasing interest in "foldamers,"
which are oligomers that adopt specific biopolymer-like shapes. The
foldamer concept constitutes the basis of a subfield of chemistry that has
germinated and grown over the past 15 years or so.
Proteins are natural oligomers that fold in specific ways, and the specific
shapes adopted by proteins are necessary for their biological functions.
Many chemists have sought to extend this relationship between folding and
function to unnatural oligomers, with the hope of achieving activities that
are not accessible via more traditional molecular design strategies.
The account summarizes work from the preceding few years that has
identified a very powerful and versatile new strategy for foldamer design.
Does it describe a new discovery, methodology, or
synthesis of knowledge?
This paper is a short review that provides a synthesis of existing
knowledge. The paper offers a concise introduction to a new approach for
the design of molecules that can display unique structural and functional
Would you summarize the significance of your paper
in layman's terms?
"Foldamer research invites one to explore many
fundamental questions relating to the way that bonding
patterns within large molecules determine overall molecular
Proteins are the workhorse molecules in biology; proteins do nearly all of
the heavy lifting, at the molecular level, within living organisms.
Developing ways to mimic proteins with synthetic molecules could lead to
new substances for important applications, such as new types of drugs to
treat human diseases and new materials for solar energy harvesting.
How did you become involved in this research, and
were there any particular problems encountered along the way?
I was drawn to this research area by a deep desire to extrapolate from, and
perhaps ultimately improve upon, the remarkable molecules that are found in
Organic chemists are very good at the design and synthesis of relatively
small molecules that perform specific tasks, such as drugs, pesticides, and
dyes. However, the central functional role of proteins in biology seems to
teach us that larger molecules are intrinsically more powerful than small
Foldamer research represents an effort to extend the well-developed
knowledge and techniques of organic chemistry to create new kinds of
molecules that adopt specific shapes, which provide a basis for new
approaches to function-based design. This area is very exciting, because
the horizons are so vast, and there are so many high-impact goals to be
Foldamer research is technically challenging, because this type of work
forces one to confront limitations in synthetic and predictive tools. For
example, chemical synthesis of proteins, which requires stepwise
introduction of many subunits in a precise order, is very challenging, and
synthesis of unnatural oligomers of comparable size is even more difficult.
Where do you see your research leading in the
Foldamer research invites one to explore many fundamental questions
relating to the way that bonding patterns within large molecules determine
overall molecular shape. However, the most vital goal for foldamer
research, at this point, is to show why this family of molecules is worthy
of study. Demonstrating worthiness will require showing how foldamers can
In my own view, which could turn out to be incorrect, the clearest path to
utility is to show that foldamers can inhibit interations between specific
pairs of biological macromolecules. It is widely recognized that inhibiting
specific protein-protein associations can be very valuable medically, but
that this goal is typically difficult to achieve, particularly via
traditional small molecule-based medicinal chemistry.
Many in the foldamer community believe that this class of molecules offers
unique opportunities for mimicry of protein recognition surfaces. Achieving
this type of activity, in a variety of systems, is a major goal in my
Do you foresee any social or political
implications for your research?
I do not see any political implications behind this work. If foldamer-based
strategies truly deliver novel and effective medicinal agents, then this
area of research will contribute to the betterment of human society.
Sam Gellman, Ph.D.
Professor of Chemistry
University of Wisconsin
Madison, WI, USA Web