Peptoids, or poly-N-substituted glycines, are a class of 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 β-peptides...

s whose side chains are appended to the nitrogen atom of the peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...

 backbone, rather than to the α-carbons (as they are in amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...


Chemical structure and synthesis

In peptoids the side chain is connected to the nitrogen of the peptide backbone, instead of the α-carbon as in peptides. Notably, peptoids lack the amide hydrogen which is responsible for many of the Secondary structure
Secondary structure
In biochemistry and structural biology, secondary structure is the general three-dimensional form of local segments of biopolymers such as proteins and nucleic acids...

 elements in peptides and proteins. Peptoids were first invented by Reyna J. Simon, Paul Bartlett and Daniel V. Santi to mimic protein/peptide products to aid in the discovery of protease-stable small molecule drugs.

Following the sub-monomer protocol originally created by Ron Zuckermann, each residue is installed in two steps: acylation
In chemistry, acylation is the process of adding an acyl group to a compound. The compound providing the acyl group is called the acylating agent....

 and displacement. In the acylation step a haloacetic acid, typically bromoacetic acid
Bromoacetic acid
Bromoacetic acid is the chemical compound with the formula CH2BrCO2H. This colorless solid is a relatively strong alkylating agent. Bromoacetic acid and its esters are widely used building blocks in organic synthesis, for example in pharmaceutical chemistry....

 activated by diisopropylcarbodiimide reacts with the amine of the previous residue. In the displacement step (a classical SN2 reaction
SN2 reaction
The SN2 reaction is a type of nucleophilic substitution, where a lone pair from a nucleophile attacks an electron deficient electrophilic center and bonds to it, expelling another group called a leaving group. Thus the incoming group replaces the leaving group in one step...

), an amine displaces the halide to form the N-substituted glycine residue. The submonomer approach allows the use of any commercially available or synthetically accessible amine with great potential for Combinatorial chemistry
Combinatorial chemistry
Combinatorial chemistry involves the rapid synthesis or the computer simulation of a large number of different but structurally related molecules or materials...


Unique characteristics

Like D-Peptides and β peptides
β-peptides consist of β amino acids, which have their amino group bonded to the β carbon rather than the α carbon as in the 20 standard biological amino acids. The only commonly naturally occurring β amino acid is β-alanine; although it is used as a component of larger bioactive molecules,...

 peptoids are completely resistant to proteolysis
Proteolysis is the directed degradation of proteins by cellular enzymes called proteases or by intramolecular digestion.-Purposes:Proteolysis is used by the cell for several purposes...

, and are therefore advantageous for therapeutic applications where proteolysis is a major issue. Since secondary structure in peptoids does not involve hydrogen bonding, it is not typically denatured
Denaturation (biochemistry)
Denaturation is a process in which proteins or nucleic acids lose their tertiary structure and secondary structure by application of some external stress or compound, such as a strong acid or base, a concentrated inorganic salt, an organic solvent , or heat...

 by solvent, temperature, or chemical denaturants such as urea
Urea or carbamide is an organic compound with the chemical formula CO2. The molecule has two —NH2 groups joined by a carbonyl functional group....

 (see details below).

Notably, since the amino portion of the amino acid results from the use of any amine, thousands of commercially available amines can be used to generate unprecedented chemical diversity at each position at costs far lower than would be required for similar peptides or peptidomimetics. To date, at least 230 different amines have been used as side chains in peptoids.


Peptoids with alpha-chiral bulky side chains are known to adopt a Polyproline
Polyproline helix
A Polyproline Helix is a type of protein secondary structure, which occurs in proteins comprising repeating proline residues. A left-handed polyproline II helix is formed when sequential residues all adopt backbone dihedral angles of roughly and have trans isomers of their peptide bonds...

-type I-like conformation. Unlike regular proteins, this structure is stable in different organic solvents, temperatures up to 75 degrees Celsius, denaturants such as 8M urea, and different ionic strengths. Different strategies have been employed to predict and characterize peptoid secondary structure, with an ultimate goal of developing fully folded peptoid protein structures.


The first demonstration of the use of peptoids was in screening a combinatorial library of diverse peptoids which yielded novel high-affinity ligands for 7-transmembrane G-protein-couple receptors.

Peptoids have been developed as candidates for a range of different biomedical applications, including antimicrobial agents and synthetic lung surfactants, as well as ligands for various proteins including Src Homology 3 (SH3 domain
SH3 domain
The SRC Homology 3 Domain is a small protein domain of about 60 amino acids residues first identified as a conserved sequence in the viral adaptor protein v-Crk and the non-catalytic parts of enzymes such as phospholipase and several cytoplasmic tyrosine kinases such as Abl and Src...

), Vascular Endothelial Growth Factor (VEGF) receptor 2,, and antibody Immunoglobulin G
Immunoglobulin G
Immunoglobulin G are antibody molecules. Each IgG is composed of four peptide chains — two heavy chains γ and two light chains. Each IgG has two antigen binding sites. Other immunoglobulins may be described in terms of polymers with the IgG structure considered the monomer.IgG constitutes 75%...

 biomarkers for the identification of Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...


Due to their advantageous charactersitics as described above, peptoids are also being actively developed for use in nanotechnology,, an area in which they may play an important role.
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