title: Azapeptides and their therapeutic potential.
abstract: Azapeptides are peptide analogs in which one or more of the amino residues is replaced by a semicarbazide. This substitution of a nitrogen for the α-carbon center results in conformational restrictions, which bend the peptide about the aza-amino acid residue away from a linear geometry. The resulting azapeptide turn conformations have been observed by x-ray crystallography and spectroscopy, as well as predicted based on computational models. In biologically active peptide analogs, the aza-substitution has led to enhanced activity and selectivity as well as improved properties, such as prolonged duration of action and metabolic stability. In light of these characteristics, azapeptides have found important uses as receptor ligands, enzyme inhibitors, drugs, pro-drugs, probes and imaging agents. Recent improvements in synthetic methods for their procurement have ushered in a new era of azapeptide chemistry. This review aims to provide a historical look at the development of azapeptide science along with a focus on recent developments and perspectives on the future of this useful tool for medicinal chemistry.
authors.affiliation: Département de Chimie, Université de Montréal, CP 6128, Succursale Centre Ville, Montréal, Québec, H3C3J7, Canada.
authors.forename: Caroline
authors.initials: C
authors.lastname: Proulx
authors.forename: David
authors.initials: D
authors.lastname: Sabatino
authors.forename: Robert
authors.initials: R
authors.lastname: Hopewell
authors.forename: Jochen
authors.initials: J
authors.lastname: Spiegel
authors.forename: Yésica
authors.initials: Y
authors.lastname: García Ramos
authors.forename: William D
authors.initials: WD
authors.lastname: Lubell
mesh_terms: D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008968:Molecular Conformation; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D012663:Semicarbazides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
chemical_list: D001372:Aza Compounds; D004791:Enzyme Inhibitors; D010455:Peptides; D012663:Semicarbazides