4-Methylpseudoproline analogues of cyclolinopeptide A: Synthesis, structural analysis and evaluation of their suppressive effects in selected immunological assays

Effects of Modifications on the Immunosuppressive Properties of Cyclolinopeptide A and Its Analogs in Animal Experimental Models

“…In a last attempt to modify the CLA structure [ 18 ], the synthesis of new analogues of cyclolinopeptide A and their linear precursors, modified with ( R )- and/or ( S )-4-methylpseudoproline in the Pro 6 -Pro 7 fragment, was performed. The structure of the peptides was also characterized by application of nuclear magnetic resonance (NMR) and circular dichroism (CD).…”

“…Another group of researchers [ 26 ] confirmed that this type of interaction is weak since the inhibition of calcineurin activity, important in T cell signaling and proliferation [ 27 ] required 10× higher concentration of CLA than for CsA or tacrolimus. Strong inhibition of mitogen induced proliferation of PBMC by CLA analogs was associated with significant changes in expression of cell signaling molecules in Jurkat T cells [ 17 , 18 ], such as block of caspase 3 responsible for activation of T cells and IL-2 production [ 28 ] and increase of Fas [ 16 ] involved in apoptosis [ 29 ]. In turn, the mechanism of action of cyclic tetrapeptide cyclo-(Pro-Pro- β 3 hPhe-Phe-) was clearly associated with its effects on prostanoid activity [ 20 ].…”

Effects of Modifications on the Immunosuppressive Properties of Cyclolinopeptide A and its Analogs in Animal Experimental Models

“…In a last attempt to modify CLA structure [18], the synthesis of new analogues of cyclolinopeptide A and their linear precursors, modified with (R)-and/or (S)-4-methylpseudoproline in the Pro 6 -Pro 7 fragment, was performed. The structure of the peptides was also characterized by application of nuclear magnetic resonance (NMR) and circular dichroism (CD).…”

“…Another group of researchers [26] confirmed that this type of interaction is weak since the inhibition of calcineurin activity, important in T cell signaling and proliferation [27] required 10 x higher concentration of CLA than for CsA or tacrolimus. Strong inhibition of mitogen induced proliferation of PBMC by CLA analogs was associated with significant changes in expression of cell signaling molecules in Jurkat T cells [17,18], such as block of caspase 3 responsible for activation of T cells and IL-2 production [28] and increase of Fas [16] involved in apoptosis [27]. In turn, the mechanism of action of cyclic tetrapeptide c(Pro-Pro-β 3 hPhe-Phe-) was clearly associated with its effects on prostanoid activity [20].…”