Synthesis of glyoxylyl peptides using an Fmoc-protected alpha,alpha'-diaminoacetic acid derivative.
The synthesis of glyoxylyl peptides by coupling the masked glyoxylic acid derivative (FmocNH)(2)CHCO(2)H, 1, to a peptidyl resin assembled using Fmoc/tert-butyl chemistry has been described recently. Deprotection and cleavage of the peptide from the solid support using TFA was followed by unmasking of the glyoxylyl group in solution in the presence of DBU. [] The glyoxylyl peptide was thus generated using non-oxidizing conditions by comparison with the method based on the periodic oxidation of a seryl-precursor. However, base treatment of the (FmocNH)(2)CHCO(2)-peptide led to the formation of a byproduct besides the desired glyoxylyl peptide. This paper describes an optimized procedure for unmasking the Fmoc-protected alpha,alpha'-diaminoacetic acid moiety in solution which suppressed byproduct formation. Also presented is a series of experiments that permitted a structure and a mechanism of formation for the byproduct to be suggested.
Far
Samia
S
UMR 8525 CNRS-Université de Lille 2, Institut de Biologie de Lille, 1 rue du Professeur Calmette, 59021 Lille, France.
Melnyk
Oleg
O
D000085:Acetates / Q000378:metabolism*; D000596:Amino Acids / Q000737:chemistry*; D000599:Amino Acids, Diamino / Q000378:metabolism*; D005449:Fluorenes / Q000737:chemistry*; D006038:Glyoxylates / Q000378:metabolism*; D006898:Hydroxylamines / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000085:Acetates; D000596:Amino Acids; D000599:Amino Acids, Diamino; D005449:Fluorenes; D006038:Glyoxylates; D006898:Hydroxylamines; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D010455:Peptides; C017064:benzyloxyamine; C031150:glyoxylic acid