Peptidic Hydrogels - In-Situ Gelling Polymers: For Biomedical Applications - page 125

interactions, as well as electrostatic interactions. In aqueous solutions, all of the
above interactions have been used, primarily in concert, in bringing peptides
together and to hold the assembled structure together after assembly and gela-
tion [ 11 , 14 , 15 , 22 , 25 - 27 , 33 , 34 , 46 - 48 ]. Change of the pH, ionic concentra-
tion, or temperature of a solution can be used to trigger the solution assembly of
the peptide sequences. These changes force single molecules to intramolecularly
fold into desired secondary structures, such as ʲ -sheets or ʱ -helices, and/or col-
lections of molecules that begin intermolecularly assembling to form local nano-
structure such as nanofibrils or nanotubes. The entire process results in a hydrogel
with quaternary structure (i.e. hydrogel network structure) organization [ 1 , 2 , 6 ,
10 - 18 , 26 , 28 , 29 , 31 , 34 - 36 , 48 - 50 ]. This chapter explores the formation of pri-
mary and secondary structures with small peptides as well as resultant, physical
hydrogels and underlying peptide tertiary and quaternary (i.e. hydrogel network)
structure.
1 Primary Structures
Primary structure is first order peptide structure—the amino acid linear sequence.
The diversity in the natural amino acids as well as numerous synthetic, non-natural
amino acids allows for a great and constantly growing number of possibilities of
primary sequences. Linked together with amide bonds between the carboxylic acid
and amine ends of neighboring amino acids, peptides are predominantly linear in
architecture although chemistry can be designed to make branched peptides, par-
ticularly when peptides are combined as a hybrid with other organic molecules.
For example, peptide primary structure can also be seen in hybrid polymer-peptide
or aliphatic hydrocarbon conjugates that can introduce new architecture and other
characteristics (e.g. peptide amphiphiles that exhibit branches or helical behavior
[ 11 , 14 - 16 , 19 - 27 , 33 , 51 - 55 ]; or polymer-peptide conjugates that have star or
branched architecture [ 17 , 18 , 28 - 35 , 56 - 62 ]). However, the focus here will be on
linear peptide architecture.
Previously, the synthesis of peptidic materials was seen as a cumbersome and
expensive method that lacked the precision of other polymeric synthesis methods
[ 3 , 10 , 13 , 16 , 18 , 33 , 36 - 38 , 63 ]. Synthesis of peptides has quickly advanced
with cheaper methods, larger yield quantities, greater precision, and more adap-
tive equipment and methodology. There are two main pathways of creating a
large number of customized peptide sequences, (a) engineered/recombinant DNA
synthesis or (b) synthetic solid phase peptide synthesis (SPPS) [ 1 , 13 , 18 , 20 , 33 ,
36 , 39 - 45 , 64 , 65 ]. These methods are preferred to traditional methods because
of the yield, automation, and time saved when compared to manual organic
synthesis.
Recombinant DNA peptide synthesis refers to the use of introducing modified
DNA to a host, typically E. coli , to subsequently produce the designed peptide