AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |
Back to Blog
Peptide backbone nitrogen atom11/23/2023 ![]() ![]() Peptoids have been developed as candidates for a range of different biomedical applications, including antimicrobial agents, synthetic lung surfactants, ligands for various proteins including Src Homology 3 ( SH3 domain), Vascular Endothelial Growth Factor ( VEGF) receptor 2, and antibody Immunoglobulin G biomarkers for the identification of Alzheimer's disease. 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. It was also found that n→π* interactions can modulate the ratio of cis/trans amide bond conformers, until reaching a complete control of the cis conformer in the peptoid backbone using a functionalizable triazolium side chain. Nonetheless, scientists were able to find trans-inducer N-Aryl side chains promoting polyproline type II helix, and strong cis-inducer such as bulky naphtylethyl and tert-butyl side chains. The cis/trans amide bond isomerization still leads to a conformational heterogeneity which doesn’t allow for the formation of homogeneous peptoid foldamers. Different strategies have been employed to predict and characterize peptoid secondary structure, with the ultimate goal of developing fully folded peptoid protein structures Nevertheless, through the choice of appropriate side chains it is possible to form specific steric or electronic interactions that favour the formation of stable secondary structures like helices, especially peptoids with C-α-branched side chains are known to adopt structure analogous to polyproline I helix. Peptoid oligomers are known to be conformationally unstable, due to the flexibility of the main-chain methylene groups and the absence of stabilizing hydrogen bond interactions along the backbone. To date, at least 230 different amines have been used as side chains in peptoids. 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. Since secondary structure in peptoids does not involve hydrogen bonding, it is not typically denatured by solvent, temperature, or chemical denaturants such as urea (see details below). Like D-Peptides and β peptides, peptoids are completely resistant to proteolysis, and are therefore advantageous for therapeutic applications where proteolysis is a major issue. The submonomer approach allows the use of any commercially available or synthetically accessible amine with great potential for combinatorial chemistry. In the displacement step (a classical S N2 reaction), an amine displaces the halide to form the N-substituted glycine residue. In the acylation step, a haloacetic acid, typically bromoacetic acid activated by diisopropylcarbodiimide reacts with the amine of the previous residue. įollowing the sub-monomer protocol originally created by Ron Zuckermann, each residue is installed in two steps: acylation and displacement. Santi to mimic protein/peptide products to aid in the discovery of protease-stable small molecule drugs for the East Bay company Chiron. Notably, peptoids lack the amide hydrogen which is responsible for many of the secondary structure elements in peptides and proteins. In peptoids, the side chain is connected to the nitrogen of the peptide backbone, instead of the α-carbon as in peptides. Peptidomimetics are recognizable by side chains that are appended to the nitrogen atom of the peptide backbone, rather than to the α-carbons (as they are in amino acids).Ĭhemical structure and synthesis Structure (top) and synthesis (bottom) of peptoids highlighting the submonomer approach. Peptoids (root from the Greek πεπτός, peptós "digested" derived from πέσσειν, péssein "to digest" and the Greek-derived suffix -oid meaning "like, like that of, thing like a _," ), or poly- N-substituted glycines, are a class of biochemicals known as biomimetics that replicate the behavior of biological molecules. JSTOR ( May 2011) ( Learn how and when to remove this template message).Unsourced material may be challenged and removed. Please help improve this article by adding citations to reliable sources. This article needs additional citations for verification. ![]()
0 Comments
Read More
Leave a Reply. |