Boc-Abu-OH.DCHA

Boc-Abu-OH.DCHA
Nα-Boc-L-2-aminobutyric acid dicyclohexylammonium salt; N-cyclohexylcyclohexanamine;(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid

Boc-L-α-aminobutyric acid (Boc-Abu-OH) isolated as its dicyclohexylamine (DCHA) salt: Boc on the α-amine, and the α-carboxyl present as a carboxylate paired with the dicyclohexylammonium cation. The α-carbon is (2S), the L configuration.

Weigh it as the salt: C9H17NO4 · C12H23N (C21H40N2O4), 384.55. The free acid is C9H17NO4, 203.24, so one mole of the protected amino acid arrives as about 384.6 g of this product against about 203.2 g of the free acid — roughly 53% of this material's mass is the protected amino acid, and a recipe written for the free acid will be short of it unless the mass is recalculated.

Before activation, convert the dicyclohexylammonium carboxylate to the neutral free acid using a validated acidification and work-up. A published procedure on a different Boc-protected amino acid DCHA salt, Z-Dab(Boc)-OH · DCHA, did this by suspending the salt in ethyl acetate and adding 1 M phosphoric acid.

In Boc/benzyl solid-phase synthesis the Nα-Boc group is removed with TFA at the start of every cycle; in situ neutralization protocols were developed for that cycle, neutralizing the TFA salt of the resin-bound amine during the coupling itself.

α-Aminobutyric acid is alanine with an ethyl side chain: one methylene longer and unbranched, with no side-chain functional group that requires protection during peptide assembly. Substituting it for cysteine or serine is a way of removing a thiol or a hydroxyl while leaving a side chain of comparable size. One demonstrated example: in the chemically synthesized HIV-1 protease whose crystal structure was solved at 2.8 Å, the cysteines had been replaced by L-α-amino-n-butyric acid and the protein was enzymatically active. What such a substitution does to folding and activity is sequence-dependent and has to be tested.

Applications

• Boc/benzyl synthesis of peptides containing L-α-aminobutyric acid, once the salt has been converted to the free acid
• Cysteine-to-Abu and serine-to-Abu substitutions
• Preparation of activated esters and dipeptide intermediates of Boc-Abu-OH

Storage
Store refrigerated (2–8 °C) in a tightly closed container, and let it reach room temperature before opening.

References

1. Faschinger F et al. Stable Europium(III) Complexes with Short Linkers for Site-Specific Labeling of Biomolecules. ChemistryOpen 2017, 6, 721–732. doi:10.1002/open.201700122
2. Schnölzer M et al. In situ neutralization in Boc‐chemistry solid phase peptide synthesis. International Journal of Peptide and Protein Research 1992, 40, 180–193. doi:10.1111/j.1399-3011.1992.tb00291.x
3. Wlodawer A et al. Conserved Folding in Retroviral Proteases: Crystal Structure of Synthetic HIV-1 Protease. Science 1989, 245, 616–621. doi:10.1126/science.2548279

For research use only. Not for human or veterinary use.