α-Chloroacetyl capping of peptides: An N-terminal capping strategy suitable for Edman sequencing

Tetrahedron Letters

Volumn 41, Issue 6, 2000, Pages 827-829

  Shogren Knaak, Michael A ^a   McDonnell, Kevin A ^a   Imperiali, Barbara ^a  

^a MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

Amino acid derivatives; Amino acids; Combinatorial chemistry; Peptides; Polypeptides; Solid phase synthesis

Indexed keywords

AMINO ACID; AMINO ACID DERIVATIVE; AMMONIA; CHLOROACETIC ACID; GLYCINE; PEPTIDE; POLYPEPTIDE;

AMINO ACID SEQUENCE; AMINO TERMINAL SEQUENCE; ARTICLE; CHEMICAL REACTION; PH; PROTEIN PROCESSING; REACTION ANALYSIS;

EID: 0034606973     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(99)02202-9     Document Type: Article

References (8)

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3. Fields, G. B.; Noble, R. L. Int. J. Peptide Protein Res. 1990, 35, 161-214.; Shogren-Knaak, M. A.; Imperiali, B. Bioorg. Med. Chem. 1999, 7, 1993-2002.
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5. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, Third Ed.; John Wiley & Sons: New York, 1999; pp. 555-556.
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7. Sequencing of the peptide beads was performed either at the Caltech Protein Microanalytical Laboratory or at the University of British Columbia Protein Service Laboratory. Individual beads were submitted whole in 1:1 methanol:water, transferred to a filter support, and sequenced on a 476A protein sequenator (Perkin Elmer/Applied Biosystems Inc.) using standard Edman degradation protocols. Hydrolysis of side chain amides has been documented following aqueous ammonia treatment. However, in our sequences this was not a concern, because no position contained both an asparagine and aspartic acid or a glutamine and glutamic acid.
8. The presence of unnatural amino acid β-diaminoproprionic acid (Dap) was inferred, because it could not be detected directly under standard sequencing conditions. Furthermore, the presence of Dap resulted in truncated side product starting from the Dap residue. This product was shown to result from the ammonia treatment, but did not occur when the Dap residue was replaced by γ-diaminobutyric acid, ornithine, or lysine amino acids. The truncated product was not the major species and did not effect the ability to assign the peptide sequence.