Author/Editor		Gobec, Stanislav; Urleb, Uroš
Title		Načrtovanje in sinteza ftalimido in adamantil substituiranih fosforjevih analogov muramil dipeptida
Type		članek
Source		In: Musar A, Florjančič U, editors. Raziskovalno delo podiplomskih študentov Slovenije: naravoslovje in tehnika. 1. dnevi podiplomskih študentov Slovenije; 2000 nov 10; Ljubljana. Ljubljana: Društvo mladih raziskovalcev Slovenije,
Publication year		2000
Volume		str. 53-64
Language		slo
Abstract		N-Acetylmuramyl-L-alanyl-D-isoglutamine (muramyldipeptide, MDP) is the smallest immunologically active peptidoglycan derivate. In order to improve its immunostimulatory activity and to reduce its unwanted toxic effects, as well as to improve its farmacokinetics, a number of MDP analogs have been prepared. It is well known that muramoyl part of MDP is not essential for its immunomodulating activity and that it can be sucessfully replaced by vrious carbocyclic, heterocyclic and acyclic groups. Phthalimido-desmuramyl dipeptides LK 413 and LK 423, as well as adamantyldesmuramyl dipeptide LK 415, showed interesting immunomodulating activity and were chosen as lead compounds. To obtain more SAR data, we have modified the peptide backbone of phthalimido and adamantyl substituted MDP analogs using various phosphours bioisosteres. We have replaced the amide bond between 5-phthalimidopentanoyl chain and alanine by methyl phosphinamide moiety. The acarboxylic group of glutamic acid has been replaced by diethyl phosphonate isostere. Some of the synthesized phosphorus MDP analogs were tested in in vitro immunological tests. They showed the ability to modulate the ionomycin & phorbol 12-myristate 13-acetate induced cytokine production potential of human peripheral blood mononuclear cells. The introduction of phosphorus isosters has been sucsessfull since the activity of tested compounds was comparable or even higher as the acivity of the lead compounds. We can conclude that phosphono desmuramyldipeptides are potential immunomodulators.
Descriptors		ADJUVANTS, IMMUNOLOGIC ACETYLMURAMYL-ALANYL-ISOGLUTAMINE TECHNOLOGY, PHARMACEUTICAL PHOSPHINES PHOSPHONIC ACIDS TUMOR NECROSIS FACTOR MONOCYTES INTERLEUKINS