Introduction: Peptides have gained renewed interest as candidate therapeutics. However, to bring them to a broader clinical use, challenges such as the rational optimization of their pharmacological properties remain. Peptide scanning techniques offer a systematic framework to gain information on the functional role of individual amino acids of a peptide. Due to progress in mastering new chemical synthesis routes targeting amino acid backbone, they are currently diversified. Structure-activity relationship (SAR) analyses such as alanine- or enantioneric- scanning can now be supplemented by N-substitution, lactam cyclisation- or aza-amino scanning procedures addressing not only SAR considerations but also the peptide pharmacological properties.
Areas covered: This review highlights the different scanning techniques currently available and illustrates how they can impact drug discovery.
Expert opinion: Progress in peptide scanning techniques opens new perspectives for peptide drug development. It comes with the promise of a paradigm change in peptide drug design in which peptide drugs will be closer to the parent peptides. However, scanning still remains assimilable to a trial and error strategy that could benefit from being combined with specific in silico approaches that start reaching maturity.
Keywords: Ala-; Aza-amino; D-; N-alkyl scanning; Peptide drug development; Peptide scanning; Positional-; Pro-; gamma-lactam.