Enkephalins stabilized

Sayani, A.P., I.K. Chnn, and Y.W. Chien, Transmucosal delivery of leucine enkephalin stabilization in rabbit enzyme extracts and enhancement of permeation through mucosae. J Pharm Sci, 1993. 82(11) 1179-85. 

Faraj et al. [28] studied the effects of different concentrations of leucine enkephalin, peptidase inhibitors, and sodium glycocholate (GC) on the stability and absorption of leucine enkephalin in nasal cavities of rats. Based on the study, the rate and extent of formation of des-tyrosine leucine enkephalin... 

Chun IK, Chien YW (1993) Transmucosal delivery of methionine enkephalin. I Solution stability and kinetics of degradation in various rabbit mucosa extracts. J Pharm Sci 82 373-378. 

In the enkephalin studies we began to see how theoretical techniques can be used to generate conformations of related molecules. With the results from GnRH and vasopressin we saw how flexible these molecules are and how the conformational fluctuations and dynamics of these molecules can be studied. We also saw how the relative stabilities of conformations of a molecular fragment can be influenced by conformational constraints of the whole molecule. In the following section we will present some ideas on how these calculations can be incorporated into a conformational based approach to drug design. 

Langoth et al. [86] studied the properties of matrix-based tablets containing the novel pentapeptide leu-enkephalin (Tyr-Gly-Gly-Phe-Leu) that has been shown to have pain-modulating properties. The matrix-based tablets were made with the thiolated polymer PCP. The covalent attachment of cysteine to the anionic polymer PCP leads to an improvement of the stability of matrix tablets, enhances the mucoadhesive properties, and increases the inhibitory potency of PCP towards buccal enzymes. All these factors lead to stability of the peptide and a controlled drug release for the peptide was obtained for more than 24 h. Also, the tablets based on thiolated PCP remained attached on freshly excised porcine mucosa 1.8 times longer than the corresponding unmodified polymer. 

Early SAR investigations revealed that the amide of Met-enkephalin was several times as active as the parent with a longer duration of action and that replacement of Gly2 by D-Ala had a similar influence on peptide stability/62,63 It was later shown that a variety of D-amino acids in place of Gly2 caused a marked increase in potency both in GPI and MVD assays, results presumed... 

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