1. 2-(N-Fmoc)-3-(N-Boc-N-methoxy)-diaminopropanoic acid, an amino acid for the synthesis of mimics of O-linked glycopeptides
Michael R Carrasco, Ryan T Brown, Vu H Doan, Sean M Kandel, Franklin C Lee Biopolymers. 2006;84(4):414-20. doi: 10.1002/bip.20496.
Amino acids with N-alkylaminooxy side chains have proven effective for the rapid synthesis of neoglycopeptides. Chemoselective reaction of reducing sugars with peptides containing these amino acids provides glycoconjugates that are structurally similar to their natural counterparts. 2-(N-Fmoc)-3-(N-Boc-N-methoxy)-diaminopropanoic acid (Fmoc: 9-fluorenylmethoxycarbonyl; Boc: t-butyloxycarbonyl) was synthesized from Boc-Ser-OH in >40% overall yield and incorporated into peptides by standard Fmoc chemistry based solid phase peptide synthesis. The resulting peptides are efficiently glycosylated and serve as mimics of O-linked glycopeptides. The synthesis of this derivative greatly expands the availability of the N-alkylaminooxy strategy for neoglycopeptides.
2. Solid-phase synthesis of a cyclic decapeptide, analog of the antibiotic polymyxin M
E E Salem Pharmazie. 1980 Dec;35(12):761-3.
Pelargonoyl-cyclo[Dab-Thr-Dab-Dab(Pel)-Dab-D-Leu-Thr-Dab-Dab-Thr]. 5 HCl (5), analog of the polymyxin M, has been synthesized by the solid phase method. The intermediate linear Boc-protected decapeptide-resin (1) was assembled on the solid support by the stepwise addition of Boc-amino acids in the presence of DCC. For side-chain protection of diaminobutyric acid, Z-group was used. The peptide was cleaved from the resin in the form of methyl ester by triethylamine-catalyzed transesterification with methanol. Alkaline hydrolysis of the peptide ester with aqueous KOH (1 mol/l) afforded the Bocpenta-benzyloxycarbonyl-decapeptide acid (2) in 60% yield (based on Thr/resin). After removal of the Boc-group, the linear peptide 3 was cyclized with DCC in high dilution in DMF (10(-3) mol/l) to give 4 in 51% yield. Hydrogenolysis of 4 in 80% formic acid afforded the pelargonyl cyclic decapeptide 5 in 74% yield. The synthetic peptide 5 retained the same activity of the natural polymyxin M against Bacillus subtilis and Staphylococcus aureus, whereas it showed only 3% of the activity of Escherichia coli.
3. Solid-phase peptide synthesis using nanoparticulate amino acids in water
Keiko Hojo, Hideki Ichikawa, Mitsuko Maeda, Shinya Kida, Yoshinobu Fukumori, Koichi Kawasaki J Pept Sci. 2007 Jul;13(7):493-7. doi: 10.1002/psc.874.
Solid-phase peptide synthesis has many advantages compared with solution peptide synthesis. However, this procedure requires a large amount of organic solvents. Since safe organic solvent waste disposal is an important environmental problem, a technology based on coupling reaction of suspended nanoparticle reactants in water was studied. Fmoc-amino acids are used widely, but most of them show low solubility in water. We prepared well-dispersible Fmoc-amino acid nanoparticles in water by pulverization using a planetary ball mill in the presence of poly(ethylene glycol). Leu-enkephalin amide was prepared successfully using the nanoparticulate Fmoc-amino acid on a poly(ethylene glycol)-grafted Rink amide resin in water.
