description

Fmoc-ACA is used for solid-phase syntheses of fluorogenic protease substrates based on 7-amino-4-carbamoylmethylcoumarin (ACC).

Fmoc-ACA can be loaded onto polystyrene Rink resin and requires three repeated couplings to achieve 89% substitution. The unreacted amine functionalities have to be capped using acetic anhydride.

(a) Rink amine resins (0.5 equiv.), DIC/HOBt, DCM/DMF (7:3 v/v), 3x 30 min, (b) Acetic Anhydride (20 equiv.), Pyridine (10 equiv.), 30 min, (c) Piperidine in DMF (1:4 v/v), 2x 5 min, 30 min.

Fmoc-ACA-OH is incorporated into peptides as Fluorogenic marker for protease substrates.

references

Fields, G. B.; Noble, R. L. 1990; 35: 161-214.

“Approaches to High Throughput Physical Organic Chemistry” Portal, C.; Bradley, M. Org. Biomol. Chem. (Emerging Areas) 2007; 5: 587-592.

Salisbury, Cleo M.; Maly, Dustin J.; Ellman, Jonathan A. Journal of the American Chemical Society (2002), 124(50), 14868-14870. DOI:10.1021/ja027477q;

Maly, Dustin J.; Leonetti, Francesco; Backes, Bradley J.; Dauber, Deborah S.; Harris, Jennifer L.; Craik, Charles S.; Ellman, Jonathan A. Journal of Organic Chemistry (2002), 67(3), 910-915. DOI:10.1021/jo016140o;

Kasperkiewicz, Paulina; Poreba, Marcin; Snipas, Scott J.; Parker, Heather; Winterbourn, Christine C.; Salvesen, Guy S.; Drag, Marcin Proceedings of the National Academy of Sciences of the United States of America (2014), 111(7), 2518-2523.
DOI:10.1073/pnas.1318548111;

Rut, Wioletta; Poreba, Marcin; Kasperkiewicz, Paulina; Snipas, Scott J.; Drag, Marcin Journal of Medicinal Chemistry (2018), 61(12), 5222-5234. DOI:10.1021/acs.jmedchem.8b00026.