Phosphorylation of enkephalins enhances their proteolytic stability.
Pharmacological action of enkephalins as opioid peptides is limited because of their rapid degradation by endoproteases. A novel approach is used in this study to prolong the life of those peptides. Phosphorylation of N-terminal tyrosine residue is found to have a profound influence in improving the stability of [Met]enkephalin and [Leu]enkephalin against the action of aminopeptidase M. Whereas, breakdown of [Met]enkephalin and [Leu]enkephalin is essentially complete in less than one min when incubated at 37 degree C with purified aminopeptidase M (EC3.4.11.2; substrate:enzyme = 1:0.1) in Tris buffer (pH 7.02), the corresponding phospho analogs are still detected 60 min after start of incubation. The rate of disappearance of phospho-[Met]enkephalin and phospho-[Leu]enkephalin follows first-order kinetics with half-lives of 7.3 and 8.3 min, respectively.
Dass
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C
Department of Chemistry, University of Memphis, TN 38152, USA.
Mahalakshmi
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P
D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004743:Enkephalin, Leucine / Q000378:metabolism; D004744:Enkephalin, Methionine / Q000378:metabolism; D004745:Enkephalins / Q000737:chemistry / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D063208:Methionyl Aminopeptidases; D008861:Microsomes / Q000201:enzymology; D008969:Molecular Sequence Data; D010766:Phosphorylation; D013379:Substrate Specificity; D013552:Swine
D004745:Enkephalins; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; D000626:Aminopeptidases; D063208:Methionyl Aminopeptidases