The emergence of biology as an engineering discipline took a major step forward
with the advent of recombinant DNA technology in the 1970s. Although the first
recombinant DNA experiments were motivated by fundamental questions about the
organization of genetic information [8], the prospect of using the technology to
make valuable proteins was appreciated very quickly [9]. Forty years later, the
global market for the products of biotechnology rivals that for polymeric materials.
By the mid-1980s, recombinant DNA technology had advanced to the point
where it could be used reliably even by investigators working in fields other than
molecular biology. For those of us in polymer chemistry, the availability of
recombinant methods created some especially important opportunities, in that it
afforded the possibility of making new macromolecules with essentially complete
control of the molecular architecture. Although it was not entirely clear how general
the method would prove to be, it seemed likely that artificial genes could be used to
direct the synthesis of a wide variety of protein-like macromolecules of defined
length, sequence, and stereochemistry. The prospect of making such well-defined
macromolecules raised important new questions about the connections between
macromolecular structure and function, and opened the door to new ways of
thinking about macromolecular design. The boundaries between natural and
synthetic polymers began to blur.
We started to think about these issues in 1986, with the objective of using artificial
genes to program both molecular and supramolecular architecture in macromolecular
systems. Our first targets, conceived and pursued with our colleagues Maurille
Fournier and Thomas Mason at the University of Massachusetts, were predetermined
crystal structures and liquid crystal phases. We were soon drawn to the design of
supramolecular gels and to analogs of extracellular matrix proteins for use in surgery
and regenerative medicine, and to the challenge of making artificial proteins from
amino acid building blocks that do not appear in natural proteins. What we did not
anticipate was that our interest in such “non-canonical” amino acids would lead us to
new ways of exploring fundamental biological questions. The following sections
describe these and related developments at the intersection of macromolecular
chemistry and biology.
2 Control of Supramolecular Architecture
and Macromolecular Materials Properties
2.1 Chain-Folded Lamellar Crystals from Periodic
Polypeptides
The widespread occurrence of chain-folded lamellar crystals in synthetic polymers
of regular structure has been known since the 1950s [10]. We wondered whether it
might be possible use artificial genetic information to program the formation of
such crystals through the design of periodic polypeptides, with control of chain
The Wonder of Life in Its Chemical Aspect
201
with the advent of recombinant DNA technology in the 1970s. Although the first
recombinant DNA experiments were motivated by fundamental questions about the
organization of genetic information [8], the prospect of using the technology to
make valuable proteins was appreciated very quickly [9]. Forty years later, the
global market for the products of biotechnology rivals that for polymeric materials.
By the mid-1980s, recombinant DNA technology had advanced to the point
where it could be used reliably even by investigators working in fields other than
molecular biology. For those of us in polymer chemistry, the availability of
recombinant methods created some especially important opportunities, in that it
afforded the possibility of making new macromolecules with essentially complete
control of the molecular architecture. Although it was not entirely clear how general
the method would prove to be, it seemed likely that artificial genes could be used to
direct the synthesis of a wide variety of protein-like macromolecules of defined
length, sequence, and stereochemistry. The prospect of making such well-defined
macromolecules raised important new questions about the connections between
macromolecular structure and function, and opened the door to new ways of
thinking about macromolecular design. The boundaries between natural and
synthetic polymers began to blur.
We started to think about these issues in 1986, with the objective of using artificial
genes to program both molecular and supramolecular architecture in macromolecular
systems. Our first targets, conceived and pursued with our colleagues Maurille
Fournier and Thomas Mason at the University of Massachusetts, were predetermined
crystal structures and liquid crystal phases. We were soon drawn to the design of
supramolecular gels and to analogs of extracellular matrix proteins for use in surgery
and regenerative medicine, and to the challenge of making artificial proteins from
amino acid building blocks that do not appear in natural proteins. What we did not
anticipate was that our interest in such “non-canonical” amino acids would lead us to
new ways of exploring fundamental biological questions. The following sections
describe these and related developments at the intersection of macromolecular
chemistry and biology.
2 Control of Supramolecular Architecture
and Macromolecular Materials Properties
2.1 Chain-Folded Lamellar Crystals from Periodic
Polypeptides
The widespread occurrence of chain-folded lamellar crystals in synthetic polymers
of regular structure has been known since the 1950s [10]. We wondered whether it
might be possible use artificial genetic information to program the formation of
such crystals through the design of periodic polypeptides, with control of chain
The Wonder of Life in Its Chemical Aspect
201