ISSN:
1075-2617
Keywords:
N-hydroxy peptides
;
peptides
;
ligands
;
MHC
;
solid-phase synthesis
;
MHC, major histocompatibility complex
;
BSA, bovine serum albumin
;
DMEM, Dulbecco s modified Eagle'rsquo;s medium
;
FITC, fluorescein isothiocyanate
;
TcR, T cell receptor, Alloc, allyloxycarbonyl
;
Bzl, benzyl
;
NMM, N-methyl morpholine
;
DIC, diisopropylcarbodiimide
;
TIS, triisopropylsilane
;
DIPEA, diisopropylethylamine
;
HOBt, 1-hydroxybenzotriazole
;
DBU, 1,8-diazabicyclo[5.4.0]undecen-7-ene
;
HATU, O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate
;
HOAt, 7-aza-1-hydroxybenzotriazole
;
CPY, carboxypeptidase Y
;
APM, aminopeptidase M
;
Chemistry
;
Biochemistry and Biotechnology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
A novel class of major histocompatibility complex class I (MHC-I) ligands containing an N-hydroxy-amide bond was designed on the basis of the natural epitope SIINFEKL, and synthesized on solid phase. The capacity of these compounds to bind to the MHC-I molecule H-2Kb and to induce T cell responses was analysed in comparison with the corresponding glycine containing variant of SIINFEKL. Binding to the MHC molecule was diminished by the N-hydroxy group at positions 2 and 3 of the oligomer and improved in the case of positions 4, 5, 6 and 7. No change was seen for position 1. The efficacy of T cell stimulation was strongly reduced by the modification of all positions except for position 1. A complete loss of activity was found for the N-hydroxy variant in positions 4 and 6. N-Hydroxy amide-containing peptides displayed an enhanced stability to enzymatic degradation. This new class of MHC ligand can become instrumental as immunomodulatory reagent in various disease situations. © 1998 European Peptide Society and John Wiley & Sons, Ltd.
Additional Material:
3 Ill.
Type of Medium:
Electronic Resource
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