MDP derivatives

Mineral Salts Immunostimulatory adjuvants Lipid particles Particulate adjuvants Mucosal adjuvants Aluminium hydroxide, aluminium phosphate, calcium phosphate Saponins (e.g., QS21), MDP derivatives, bacterial DNA (CpG oligos), LPS, MPL and synthetic derivatives, lipopeptides, cytokines (e.g., GM-CSF, IL-2, IL-12) Liposomes, virosomes, iscoms, cochleates, emulsions (e.g., Freunds adjuvant, SAF, MF59 ) Poloxamer particles, virus-like particles, PLG microparticles Cholera toxin (CT), mutant toxin (e.g., LTK63, LTR72), heat labile enterotoxin (LT), microparticles, polymerized liposomes, chitosan... 

Indeed, lecithin-cholesterol liposomes successfully substituted for mineral-oil emulsion in the induction of delayed hypersensitivity In guinea pigs, administration of liposome-suspensions containing MDP and ovalbumin induced delayed skin reactivity similar to that observed following immunization in MDP-supplemented incomplete Freund s adjuvant (IFA) or in CFA.30,45 However, 6-0-acyl-MDP derivatives of appropriate fatty acid chain length (Cx2-C22> i 2, 3A), but not C2-C8 (9, 1, JJJ, showed in-... 

MDP-derivatives with high (A), intermediate/marginal (B) or absent (C) adjuvant activity (as assessed by induction of manifestations of cell-mediated immunity by MDP-supplemented antigen-water-in-oil emulsions in guinea pigs). 

The peptidoglycan and fragments of it exhibit pronounced immno-stimulatory properties. The minimal structure required for the immuno-stimulation is a muramyl dipeptide (MDP, A -acetylmuramyl-L-Ala-y-D-Gln). Many investigations were directed towards the synthesis of derivatives of MDP. Fukase et al. have synthesized several MDP derivatives, as well as polymeric MPP derivative (compounds 24-29) 14, 15) in these efforts. 

Similarly, Hasegawa and co-workers have prepared and tested the immunoadjuvant activity of sulphur-containing MDP-analogues, Including lipophilic N-octadecanoyl-l-thio-derlvatives, some with additional octadecanoyl moieties on S-1 and/or 0-6, 3-deoxy 3-thlo-MDP, and 6-S-acetyl, -octadecyl, and -octadecanoyl-6-deoxy -6-thlo-MDP derivatives. The N-acetyl-muramlc acid lactones (76) yield the corresponding HO-4 unsubstituted methyl esters with retention of the D-gluco-conflguratlon, on silica gel-catalyzed methanolysis In the presence of Imidazole, lactones (76, R H... 

Muramyl dipeptide derivatives have also been microencapsulated in lactide/glycolide copolymers for use alone as an immuno potentiator. L-lactide/glycolide copolymers were used to deliver MDP-B30, a lipophilic compound, from very small microspheres (less than 5 pm in diameter). The amount of MDP-B30 required for tumor growth inhibitory activity of mouse peritoneal macrophages was 2000 times less for the controlled release MDP-B30 microspheres than for the unen-capsulated drug (134). 

A number of derivatives were synthesized in the hope of identifying a modified form that retained its adjuvanticity but displayed lesser toxicity. Some such derivatives, most notably threonyl-MDP, muramyl tripeptide and murabutide, display some clinical promise in this regard. 

This patient, who had autosomal dominant polycystic kidney disease (ADPKD), almost drowned and then developed ALPE. On July 20, 1990, he nearly drowned in the sea at 1500 hours, and was brought to our hospital by ambulance for dyspnea and severe loin pain at 1620 hours. On admission, metabolic acidosis was observed. His CRP, serum creatinine, CPK, amylase, and urinary protein levels were 1+, 1.5mg/dl, 116 U/l, 592IU/1 (derived from the salivary gland), and 2+, respectively. His body temperature was 37.7°C, and his blood pressure was 110/60 mmHg. His pulse and respiratory rate were 120/min and 22/min, respectively. Delayed CT 6h after the administration of contrast medium showed wedge-shaped contrast enhancement in the noncystic renal parenchyma (Fig. 34). On July 24, a bone scan with MDP revealed patchy lesions (Fig. 35). His serum creatinine level was 1.3 mg/dl, which had decreased to 1.0 mg/dl on July 27. The patient was then discharged. 

Recently, the Leu-enkephalin analog containing a novel derivative of Dmt lacking a basic amine [(2(S )-2-methyl-3-(2,6-dimethyl-4-hydroxyphenyDpropanoic acid, (2S)-Mdp, Fig. 7.431 was reported this peptide is an antagonist in both the MVD and GPI smooth muscle preparations, with fivefold higher potency in the MVD (739). 

Upon systemic administration, muramyldipeptides were shown to stimu-late also non-specific host resistance. MDP and various derivatives (administered in saline) (i, 5., 2, 28.3 1, 39 1) were found to protect... 

Anhydro Alditols. - A standard procedure has been used to convert the glucosamine derivative (13) to its 1,2-dideoxy analogue, and then to prepare the glycoprotein 1-deoxy-MDP and some other lipo-... 

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