Biological activity of analogues and derivatives of muramyl dipeptide

Peptidoglikani su polimeri građeni od ponavljajućih molekula N-acetilglukozamina i N-acetilmuraminske kiseline koji su međusobno povezani β-glikozidnom vezom te umreženi putem kratkih peptida. Njihovom razgradnjom nastaju manji fragmenti, tzv. muramil-peptidi, od kojih je najmanja strukturna jedinica koja posjeduje adjuvantsku aktivnost muramil-dipeptid [N-acetilmuramil-L-alanil-D-isoglutamin (MurNAc-L-Ala-D-iGln)]. S obzirom da može izazvati snažni humoralni ili stanični imunološki odgovor, upotreba muramil-dipeptida kao adjuvanta je od iznimne važnosti, te se često koristi za povećanje djelotvornosti lijekova i cjepiva. Do sada su kao lijek odobreni GMDP, Muroctasin, Murabutid, Mifamurtid i dr., a velik broj analoga i derivata podvrgnut je kliničkim ispitivanjima. Osim iznimne adjuvantske aktivnosti, prisutnost muramil-dipeptida odgovorna je za modulaciju mnogobrojnih bolesti kao što su Crohnova bolest, Alzheimerova bolest te kod stvaranja osteoklasta.Peptidoglycans are polymers built from repeating molecules of N-acetylglucosamine and N-acetylmu-ramic acid, which are attached to each other by β-glycosidic bonds and bridged by short peptides. Degradation of peptidoglycan chain results in smaller fragments, so-called muramyl peptides. The smallest structural unit possessing adjuvant activity is muramyl dipeptide [N-acetylmuramyl-L-alanyl-D-isoglu-tamine (MurNAc-L-Ala-D-iGln)]. Administration of muramyl dipeptide as an adjuvant is extremely important and is often used to increase the effectiveness of drugs and vaccines, because of its strong humoral or cellular immune response. Up to this point, GMDP, Muroctasin, Murabutid, Mifamurtid, etc. have been approved as drugs, and a large number of analogues and derivatives have undergone clinical trials. In addition to exceptional adjuvant activity, the presence of muramyl dipeptide is responsible for the modulation of numerous diseases such as Crohn's disease, Alzheimer's disease, and the formation of osteoclasts