Effect of recombinant Lactococcus lactis producing myelin peptides on neuroimmunological changes in rats with experimental allergic encephalomyelitis.

Multiple sclerosis (MS) is a human autoimmune neurodegenerative disease with an unknown etiology. Despite various therapies, there is no effective cure for MS. Since the mechanism of the disease is based on autoreactive T-cell responses directed against myelin antigens, oral tolerance is a promising approach for the MS treatment.

The biological consequences of replacing hydrophobic amino acids in deltorphin I with amphiphilic alpha-hydroxymethylamino acids.

New analogues of deltorphin I (DT I), in which the Phe residue in position 3, and the Val residue in position 5 or 6 are replaced with respective amphiphilic alpha-hydroxymethylamino acid residues (HmAA), were synthesized and tested for receptor affinity and selectivity to mu and delta opioid receptors. The analogue with (R)-HmPhe at position 3 lost receptor selectivity, as a result of a partial decrease of affinity to delta and a significant increase of affinity to mu receptors. In contrast, an analogue with (S)-HmPhe in the same position, was very potent and more specific to delta receptors than parent DT I.

Synthesis and binding properties of deltorphin I analogues containing (R) and (S)-alpha-hydroxymethylnaphtylalanine.

New analogues of deltorphin I (DT I), in which the phenylalanine residue in position 3 is substituted with amphiphilic alpha,alpha-disubstituted amino acid enantiomers, (R) and (S)-alpha-hydroxymethylnaphtylalanine, were synthesized and tested for mu and delta opioid receptor affinity and selectivity. Although both analogues have lower affinity to delta receptors than DT I, they both expressed specificity to delta receptors.

Biological activity of fragments and analogues of the potent dimeric opioid peptide, biphalin.

The synthesis and biological activity of two fragments of the very potent opioid peptide biphalin, showed that Tyr-D-Ala-Gly-Phe-NH-NH<-Phe is the minimal fragment necessary to express equal affinities and the same biological activity profile as the parent biphalin. The replacement of N'-Phe with other L- or D- lipophilic amino acids showed the possibility of modification of receptor efficacy of the analogues.