Synthesis of a positional scanning library of pentamers of N-alkylglycines assisted by microwave activation and validation via the identification of trypsin inhibitors.
A positional scanning library of 625 N-alkylglycine pentamers has been synthesized on solid-phase, employing a set of 10 commercially available primary amines as a source of chemical diversity. The iterative synthetic steps were carried out in tea bags and accelerated by using microwave assisted organic synthesis (MAOS). The reactivity study of the primary amines used as diversity sources led to determine their relative reactivity values and equireactivity factors, which were applied to the library synthesis to ensure comparable concentrations of all final oligomers in the mixtures. This library was validated by the screening, deconvolution, and identification of trypsin inhibitors. These compounds are of potential interest for controlling the intracellular transport of TRPV1 channel.
Department of Chemical and Biomolecular Nanotechnology, Instituto de Quimica Avancada de Catalunya (IQAC), CSIC, Jordi Girona 18, 08034 Barcelona, Spain.
Joaquim
J
Messeguer
Nuria
N
Cortés
Nuria
N
García-Sanz
Gloria
G
Navarro-Vendrell
Antonio
A
Ferrer-Montiel
Angel
A
Messeguer
D020650:Combinatorial Chemistry Techniques; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005998:Glycine; D008872:Microwaves; D009842:Oligopeptides / Q000138:chemical synthesis*; D054852:Small Molecule Libraries / Q000138:chemical synthesis*; D050916:TRPV Cation Channels / Q000378:metabolism; D014361:Trypsin Inhibitors / Q000138:chemical synthesis*
D009842:Oligopeptides; D054852:Small Molecule Libraries; D050916:TRPV Cation Channels; D014361:Trypsin Inhibitors; D005998:Glycine