Ipeptiden

Ipeptiden are peptides distinguished by a noncanonical isopeptide bond that links residues through side-chain groups rather than the standard alpha-carboxyl to alpha-amino linkage. In some studies, 'ipeptide' describes engineered or naturally occurring peptides in which an isopeptide bond forms between the side chain of one residue (often lysine, aspartate, or glutamate) and the main-chain carboxyl or amino group of another residue. This bond type can alter topology and increase chemical stability, contributing to protease resistance and modified binding properties.

They can be linear or cyclized and may include nonstandard amino acids or chemical linkers to promote specific conformations. Lengths range from short tetrapeptides to longer sequences. Synthesis typically uses solid-phase methods with orthogonal protecting groups to enable selective isopeptide bond formation, followed by purification and characterization. In nature, isopeptide bonds occur in post-translational modifications, and engineering approaches draw on native chemical ligation and peptide-chemistry techniques.

Applications include protease-resistant ligands, affinity reagents, and scaffolds for drug delivery or biomaterials. The altered backbone can affect receptor interactions, stability, and self-assembly. Limitations include synthetic complexity, potential immunogenicity, and the need for detailed structural verification to confirm connectivity.

See also: isopeptide, peptide bond, native chemical ligation.