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Clicked peptide polymers are poly-
The second modification required is the addition of an azide to the N-terminus. Unlike the addition of the alkyne this can be done on the whole peptide, or solely on the N-terminal residue which is added to the rest of the oligopeptide by solid-phase 
For example, if the first residue is a phenylalanine then the enzyme
triazole
A triazole is a heterocyclic compound featuring a five-membered ring of two carbon atoms and three nitrogen atoms with molecular formula C2H3N3. Triazoles exhibit substantial isomerism, depending on the positioning of the nitrogen atoms within t ...
-poly-peptide
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides.
A ...
hybrid polymers. They are made of repeating units of a 1,2,3-triazole and an oligopeptide
An oligopeptide, often just called peptide ('' oligo-'', "a few"), consists of two to twenty amino acids and can include dipeptides, tripeptides, tetrapeptides, and pentapeptides. Some of the major classes of naturally occurring oligopeptides incl ...
. They can be visualized as an oligopeptide that is flanked at both the C-terminus
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
and N-terminus
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...
by a triazole molecule.
Synthesis
Clicked peptide polymers are prepared by theazide-alkyne Huisgen cycloaddition
The azide-alkyne Huisgen cycloaddition is a 1,3-dipolar cycloaddition between an azide and a terminal or internal alkyne to give a 1,2,3-triazole. Rolf Huisgen was the first to understand the scope of this organic reaction. American chemist Karl ...
also called the click reaction; which is commonly used in bioconjugation
Bioconjugation is a chemical strategy to form a stable covalent link between two molecules, at least one of which is a biomolecule.
Function
Recent advances in the understanding of biomolecules enabled their application to numerous fields like ...
reactions to link molecules together with a stable triazole
A triazole is a heterocyclic compound featuring a five-membered ring of two carbon atoms and three nitrogen atoms with molecular formula C2H3N3. Triazoles exhibit substantial isomerism, depending on the positioning of the nitrogen atoms within t ...
bridge. Peptide based polymers are produced from a cycloaddition variant of step-growth polymerization
Step-growth polymerization refers to a type of polymerization mechanism in which bi-functional or multifunctional monomers react to form first dimers, then trimers, longer oligomers and eventually long chain polymers. Many naturally occurring a ...
. The monomers used in this polymerization are oligopeptides with terminal azide
In chemistry, azide is a linear, polyatomic anion with the formula and structure . It is the conjugate base of hydrazoic acid . Organic azides are organic compounds with the formula , containing the azide functional group. The dominant applic ...
and terminal alkyne
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Acetylene
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Propyne
\ce
\ce
\ce
\ce
1-Butyne
In organic chemistry, an alkyne is an unsaturated hydrocarbon containing at least one carbon—carbon triple bond. The simplest acyclic alkynes with only one triple bond and n ...
groupsvan Dijk, M., Nollet, M., Weijers, P., Dechesne, A., van Nostrum, C., Hennink, W., Rijkers, D., and Liskamp, R. (2008), Synthesis and Characterization of Biodegradable Peptide-Based Polymers Prepared by Microwave-Assisted Click Chemistry. Biomacromolecules, 10: 2834-2843
Monomer preparation
To prepare and oligopeptide with both a terminal azide and terminal alkyne two modifications must be carried out. The first is the amidation of the oligopeptide's C-terminus by propargylamine. This would done with all other reaction groups protected and with the C-terminus activated.
The second modification required is the addition of an azide to the N-terminus. Unlike the addition of the alkyne this can be done on the whole peptide, or solely on the N-terminal residue which is added to the rest of the oligopeptide by solid-phase peptide synthesis
In organic chemistry, peptide synthesis is the production of peptides, compounds where multiple amino acids are linked via amide bonds, also known as peptide bonds. Peptides are chemically synthesized by the condensation reaction of the carboxyl ...
. The addition of the azide occurs by Cu(II)-catalyzed diazo transfer.Alper, P. B.; Hung, S.-C.; Wong, C.-H. Tetrahedron Lett. (1996), 37, 6029-6032
Degradation
The molecules linked to one another by the azide-alkyne Huisgen cycloaddition are connected by an aromatic triazole which is extremely stable, and can withstand high temperatures and extremes of pH. The oligopeptide units of a clicked peptide polymer are a different story. The triazole bridges do not confer any stability to oligopeptide. Degradation of the polymer occurs at the peptide bonds linking individual amino acids. The amide bonds can be attacked non-specifically by acid or base catalyzedhydrolysis
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...
.
The polymer's peptide bonds can also be attacked by endopeptidase
Endopeptidase or endoproteinase are proteolytic peptidases that break peptide bonds of nonterminal amino acids (i.e. within the molecule), in contrast to exopeptidases, which break peptide bonds from end-pieces of terminal amino acids. For this re ...
s which will cleave at a specific side of a specific peptide bond based upon the residues which make up that bond.
For example, if the first residue is a phenylalanine then the enzyme chymotrypsin
Chymotrypsin (, chymotrypsins A and B, alpha-chymar ophth, avazyme, chymar, chymotest, enzeon, quimar, quimotrase, alpha-chymar, alpha-chymotrypsin A, alpha-chymotrypsin) is a digestive enzyme component of pancreatic juice acting in the duodenu ...
will cleave at site 1, and if the third residue of the tripeptide is a lysine then trypsin
Trypsin is an enzyme in the first section of the small intestine that starts the digestion of protein molecules by cutting these long chains of amino acids into smaller pieces. It is a serine protease from the PA clan superfamily, found in the dig ...
would cleave at the third cleavage site.
See also
*Biodegradable polymer
Biodegradable polymers are a special class of polymer that breaks down after its intended purpose by bacterial decomposition process to result in natural byproducts such as gases ( CO2, N2), water, biomass, and inorganic salts. These polymers ar ...
*Peptide nucleic acid
Peptide nucleic acid (PNA) is an artificially synthesized polymer similar to DNA or RNA.
Synthetic peptide nucleic acid oligomers have been used in recent years in molecular biology procedures, diagnostic assays, and antisense therapies. Due to ...
*Peptide synthesis
In organic chemistry, peptide synthesis is the production of peptides, compounds where multiple amino acids are linked via amide bonds, also known as peptide bonds. Peptides are chemically synthesized by the condensation reaction of the carboxyl ...
*Peptidomimetic
A peptidomimetic is a small protein-like chain designed to mimic a peptide. They typically arise either from modification of an existing peptide, or by designing similar systems that mimic peptides, such as peptoids and Beta-peptide, β-peptides. ...
References
{{Reflist Peptides Organic polymers Triazoles