Organometallic Derivatives of Enkephalins

For all enkephalin conjugates, we have determined the water/octanol partition coefficient (log P values) [61]. These values are a relative measure of lipophilicity of a compound. It must be noted that enkephalin as such is not able to cross the blood-brain barrier (BBB), very likely because of its fairly polar nature. It is only released in the CNS in proximity to the receptors from a larger peptide called preenkephalin. In comparison, the conjugates 27-29 are much more lipophilic, with log P values over 3.5 for 27 and 3.0 for the Mo complex 29. No difference in log P was found between the enkephalin diastereomers with Mo complexes derived from L-His or D-His. 

Sergheraert s group also attempted the synthesis of an enkephalin derivative with the organometaUic amino acid cyclobutadiene iron tricarbonyl alanine 26 [73]. This compoimd, however, did not withstand the conditions of solid phase peptide synthesis and could not be isolated in pure form. 

---