Azapeptides and their therapeutic potential

Future Medicinal Chemistry
Caroline ProulxWilliam D Lubell

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.

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Citations

Jan 23, 2014·Chemical Reviews·Miriam Góngora-BenítezFernando Albericio
Jul 22, 2011·Journal of Medicinal Chemistry·Carine B BourguetWilliam D Lubell
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Methods Mentioned

BETA
x-ray crystallographic
acylation
NMR
circular dichroism
x-ray crystallography

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