Poster Presentation 5th Modern Solid Phase Peptide Synthesis Symposium 2015

Native chemical ligation to minimize aspartimide formation: NMR comparison between regioselective and oxidative folding (#60)

Julien Tailhades 1 , Ashish Sethi 2 , Emma Petrie 3 , Paul Gooley 2 , Ross A Bathgate 1 , John D Wade 1 , M. Akhter Hossain 1
  1. The Florey Institute of Neuroscience, Parkville, VIC, Australia
  2. University of Melbourne, Parkville, VIC, Australia
  3. Walter Eliza Hall Institute, Parville, VIC, Australia

The inhibition of relaxin family peptide receptor (RXFP1) by a small LDLa protein may be a potential approach for prostate cancer treatment.1 However, it is a great challenge to chemically produce the 41-residue and three-disulfide cross-bridged LDLa module which is highly prone to aspartimide formation. The synthetic LDLa was obtained by regioselective disulfide bond formation and oxidative folding after the synthesis of the linear peptide by native chemical ligation. Both LDLa peptides were then characterized by NMR spectroscopic structural analysis after chelation with a Ca2+ ion and confirmed to be equivalent to the same protein obtained by recombinant DNA production.2 

  1. Scott, D.J., Layfield, S., Yan, Y., Sudo, S., Hsueh, A.J.W., Tregear, G.W., Bathgate, R.A.D. (2006). J. Biol. Chem. 281, 34942 – 34954.
  2. Hopkins, E.J., Layfield, S., Ferraro, T., Bathgate, R.A.D., Gooley, P.R. (2007). J. Biol. Chem. 282, 4172 – 4184.