Silver-catalyzed azaGly ligation. Application to the synthesis of azapeptides and of lipid-peptide conjugates.
Glycine is a amino acid frequently found in peptides. Substitution of a glycine residue by an azaglycine allows the modulation of peptide conformation, bioactivity, or stability. Azapeptides are usually prepared using solid-phase synthetic procedures. We show here that azaGly peptides can be assembled chemoselectively and without racemization using unprotected peptide fragments by silver-catalyzed reaction of C-terminal peptide hydrazides with N-terminal phenylthiocarbonyl peptides. The reaction was performed in a tBuOH/water mixture and the control of apparent pH permitted the clean formation of the azaGly bond in the presence of lysine residues. We show also that this novel ligation method, called azaGly ligation, can be used for the assembly of lipopeptides. For this, lipid hydrazides were reacted with a phenylthiocarbonyl peptide in the presence of silver ions. This ligation method allows incorporation of acid-sensitive lipid moieties that are incompatible with standard solid-phase peptide synthesis procedures, and more generally should be of interest for the modification of peptides by sensitive acyl moieties.
Ollivier
Nathalie
N
UMR 8161 CNRS/Universite de Lille 1 et 2, Institut Pasteur de Lille, IFR 142 Institut de Biologie de Lille,1 rue du Pr Calmette, 59021 Lille Cedex, France.
Besret
Soizic
S
Blanpain
Annick
A
Melnyk
Oleg
O
D000595:Amino Acid Sequence; D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D002384:Catalysis; D005998:Glycine / Q000138:chemical synthesis / Q000737:chemistry*; D008055:Lipids / Q000138:chemical synthesis / Q000737:chemistry*; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D012834:Silver / Q000737:chemistry*
D001372:Aza Compounds; D008055:Lipids; D010455:Peptides; D012834:Silver; D005998:Glycine