Progress with peptide scanning to study structure-activity relationships: the implications for drug discovery.
BACKGROUND
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.


METHODS
This review highlights the different scanning techniques currently available and illustrates how they can impact drug discovery.


CONCLUSIONS
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.
a INSERM UMR-S 973 , University Paris-Diderot, Sorbonne Paris Cité , Paris , France.
Stéphanie
S
Eustache
b INSERM U982 , Regional Platform for Cell Imaging of Normandy (PRIMACEN), University Rouen-Normandy , Mont-Saint-Aignan, France.
Jérôme
J
Leprince
a INSERM UMR-S 973 , University Paris-Diderot, Sorbonne Paris Cité , Paris , France.
Pierre
P
Tufféry
D000596:Amino Acids / Q000737:chemistry; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000596:Amino Acids; D010455:Peptides
Ala-; Aza-amino; D-; N-alkyl scanning; Peptide drug development; Peptide scanning; Positional-; Pro-; gamma-lactam