Analogues of muramyl dipeptide (MDP) and tuftsin limit infection and inflammation in murine model of sepsis

Dissociated Induction of Cytotoxicity and DTH by CFA and CpG

“…Owing to the potency shown by CFA in immunologic models, there are many efforts to replicate its effects using its less toxic, yet adjuvant-active components such as muramyl dipeptide, monophosphoryl lipid A, and trehalose dimycolate. [96][97][98][99][100][101][102] In light of our data showing that CFA is not merely a Th1 polarizing adjuvant but also a potent inducer of IL-17 immunity and DTH (functions not shared by CpG and possibly many other type-1 adjuvants), it would be important to continue extending the scope for searching for CFA-like adjuvants in humans which share this IL-17 polarizing activity. This would be crucial in mediating defense against many bacterial, mycobacterial, and fungal infections, protection from which, has now been shown to rely heavily on IL-17.…”

Synthesis of linear tuftsin analogues modified at the ε-amino group of lysine

“…5 To date, many retro-tuftsin analogues that have demonstrated very encouraging results have been synthesized but there is still wide scope for further research. 4,6 In current studies, tuftsin analogues containing an isopeptide bond have shown increased resistance in relation to tuftsin. The introduction of an additional residue at the e-amino group of lysine via -NH-CO-formation has led to the isopeptide bond becoming stronger than the peptide bond in the central chain.…”

“…Tuftsin is localized in a heavy chain of immunoglobulin G and is liberated by the action of two specific enzymes, leukokininase (Lys 288 -Thr 289 ) and spleen tuftsin endocarboxypeptidase (Arg 292 -Gly 293 ). [1][2][3][4][5][6] Tuftsin can activate several elements of the immune system such as granulocytes and macrophages. It has been investigated not only in bacterial infections caused by Staphylococcus aureus, Listeria monocytogenes, Escherichia coli and Serratia marcescens but also as a co-administration agent with antibiotics against opportunistic infections and has demonstrated beneficial results.…”

“…These include changing the length of the central chain and modifying the sequence of amino acids in the primary structure of tuftsin. 3,4,6 Promising results were dependent on peptide resistance against enzymatic cleavage. [3][4][5]14 Interestingly, recent research has proved that retro-tuftsin analogues significantly surpass tuftsin in both stability and activity.…”

“…3,4,6 Promising results were dependent on peptide resistance against enzymatic cleavage. [3][4][5]14 Interestingly, recent research has proved that retro-tuftsin analogues significantly surpass tuftsin in both stability and activity. 5 To date, many retro-tuftsin analogues that have demonstrated very encouraging results have been synthesized but there is still wide scope for further research.…”