An Efficient Fmoc Solid-Phase Synthesis of an Amphiphile of the Neuroprotective Agent Glycyl-prolyl-glutamic Acid

Abstract

An improved solid-phase synthesis of the neuroprotective tripeptide, glycyl-prolyl-glutamic acid, bearing a hydrophobic tail to create an amphiphile is described. The new solid-phase synthesis was adapted to prepare several analogues bearing differing hydrophobic tails.

Key words

self-assembly - peptide - Fmoc SPPS - esterification - Glypromate^®

• References

• 1 Craik DJ, Fairlie DP, Liras S, Price D. Chem. Biol. Drug Des. 2013; 81: 136
• 2 Nester J. Curr. Med. Chem. 2009; 16: 4399
• 3 Son SJ, Brimble MA, Yang S, Harris PW. R, Reddingius T, Muir BW, Hutt OE, Waddington L, Guan J, Savage GP. Aust. J. Chem. 2013; 66: 23
• 4a Patel D, McKinley BD, Davis TP, Porreca F, Yamamura HI, Hruby VJ. Bioconjugate Chem. 1997; 8: 434
• 4b Adhikari R, Francis CL, Simpson GW, Yang Q. Aust. J. Chem. 2002; 55: 629
• 5 Fields GB, Noble RL. Int. J. Pept. Protein Res. 1990; 35: 161
• 6 Harris PW. R, Yang S, Brimble MA. Tetrahedron Lett. 2011; 52: 6204
• 7 Albericio F, Barany G. Int. J. Pept. Protein Res. 1985; 26: 92
• 8 Neises B, Steglich W. Angew. Chem., Int. Ed. Engl. 1978; 17: 522
• 9a Joshi BP, Kim J.-M, Lohani CR, Cho H, Lee K.-H. Tetrahedron Lett. 2008; 49: 98
• 9b Pederson SL, Tofteng AP, Malik L, Jensen KJ. Chem. Soc. Rev. 2012; 41: 1826
• 10 Dhimitruka I, SantaLucia JJr. Org. Lett. 2006; 8: 47