Improved Fmoc-based solid-phase synthesis of homologous peptide fragments of human and mouse prion proteins.
The synthesis of difficult peptide sequences has been a challenge since the very beginning of SPPS. The self-assembly of the growing peptide chains has been proposed as one of the causes of this synthetic problem. However, there is an increasing need to obtain peptides and proteins that are prone to aggregate. These peptides and proteins are generally associated with diseases known as amyloidoses. We present an efficient SPPS of two homologous peptide fragments of HuPrP (106-126) and MoPrP105-125 based on the use of the PEGA resin combined with proper coupling approaches. These peptide fragments were also studied by CD and TEM to determine their ability to aggregate. On the basis of these results, we support PEG-based resins as an efficient synthetic tool to prepare peptide sequences prone to aggregate on-resin.
Grillo-Bosch
Dolors
D
Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac 10, E-08028 Barcelona, Spain.
Rabanal
Francesc
F
Giralt
Ernest
E
D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D005449:Fluorenes / Q000737:chemistry*; D006801:Humans; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis*; D011092:Polyethylene Glycols / Q000737:chemistry*; D000072002:Prion Proteins; D011328:Prions / Q000138:chemical synthesis* / Q000737:chemistry / Q000235:genetics; D017386:Sequence Homology, Amino Acid
C496789:9-fluorenylmethoxycarbonyl; D005449:Fluorenes; C512656:PRNP protein, human; D010446:Peptide Fragments; D000072002:Prion Proteins; D011328:Prions; C512657:Prnp protein, mouse; D011092:Polyethylene Glycols