New convenient synthesis of immunostimulating peptides containing meso-diaminopimelic acid. Syntheses of FK-565 and FK-156.
A new improved synthesis of two immunostimulating peptides: FK-156 (D-lactyl-alanyl-gamma-D-glutamyl-(L)-meso-2,6-diaminopimelyl-(L)- glycine) and FK-565 (heptanoyl-gamma-D-glutamyl-(L)-meso-2,6-diaminopimelyl-(L)- D-alanine) is described. A proper differentiation between the two chiral amino acid moieties of diaminopimelic acid was accomplished by selective enzymatic hydrolysis of one methyl ester group of the L-centre of Z2-meso-A2pm(OMe)2 (2). Utilization of a commercially available protease and diester 2 as an enzyme substrate made possible the relatively simple synthesis of a key intermediate 4 and considerably simplified the final deprotection steps. Aminolysis of the N-carboxyanhydride (4) with D-AlaONBzl or GlyONBzl was chosen to obtain the appropriate dipeptides with one free amino group as convenient intermediates for further peptide synthesis. The BOP reagent, used for peptide bond formation, secured good yields and high chemical and chiral purity of the peptides. A modification of alanine deamination procedure leading to a significant increase of D-Lac(OAc) yield is presented.
Kolodziejczyk
A M
AM
Department of Biochemistry, Medical College of Ohio, Toledo.
Kolodziejczyk
A S
AS
Stoev
S
S
D000276:Adjuvants, Immunologic / Q000032:analysis / Q000138:chemical synthesis*; D002851:Chromatography, High Pressure Liquid; D003960:Diaminopimelic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D006868:Hydrolysis; D009842:Oligopeptides / Q000138:chemical synthesis*
D000276:Adjuvants, Immunologic; D009842:Oligopeptides; D003960:Diaminopimelic Acid; C034330:FK 156; C039537:heptanoyl-gamma-D-glutamyl-L-meso-diaminopimelyl-D-alanine