Original scientific paper

In Vitro Enzymatic Stabilities of Methionine-enkephalin Analogues Containing an Adamantane-type Amino Acid

Maja Roščić ; Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Zagreb, Croatia
Vanja Sabljić ; Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Zagreb, Croatia
Kata Mlinarić-Majerski ; Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Zagreb, Croatia
Štefica Horvat ; Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Zagreb, Croatia

Abstract

The enzymatic stability of synthetic methionine-enkephalin peptide analogues containing an
unnatural amino acid of the adamantane-type 3-5 was examined in human serum, at 37 °C, and
compared with the results of the degradation of the parent endogenous pentapeptide 1 and
the tripeptide, Tyr-Gly-Gly (2). Methionine-enkephalin (Tyr-Gly-Gly-Phe-Met, 1) and tripeptide
2 are rapidly degraded in 80 % human serum with half-lives of 12.2 and 23.0 minutes, respectively,
preferably by aminopeptidase cleavage of the N-terminal Tyr-Gly peptide bond. Incorporation
of the rigid and sterically hindered 1-adamantylglycine moiety into the peptide
sequence resulted in increased stability of compound 3, while compounds 4a and 5a were not
at all susceptible to the enzymes present in human serum. Strong binding of peptides 3-5 to human
serum proteins was demonstrated.

Keywords

adamantane; enzymatic stability; human serum; methionine-enkephalin; peptide; unnatural amino acid

Hrčak ID:

31190

URI

https://hrcak.srce.hr/31190

Publication date:

31.12.2008.

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