Peptidomimetics are the molecules bearing identifiable resemblance to peptides, that as ligands of biological receptors can imitate or inhibit the effect of natural peptides. Many of the D-amino acids can be incorporated in place of the natural L-amino acids, either at a specific position, or throughout the whole peptide to increase peptides stability to ward proteases. Nonnatural amino acids may also increase in vivo half life time and potency of peptides[1,2]. Because of the non-polar nature and steric bulkiness of its side chain phenylalanine is one of the preferred amino acids in peptidomimetics. Such bioactive peptides as: third-generation modified GnRH antagonist (Cetrorelix), antibiotics (Bacitracine A, Gramicidine S), synthetic somatostatin analogue (Octreotide) are containing D-phenylalanine and its derivatives [3,4]. Predicting that pharmaceutical demand in this field may expand we have obtained following D-phenylalanine derivatives using enzymatic hydantoinase method:

Hydantoinase method consist of three steps: 1. chemical and/or enzymatic racemisation of D,L-5-substituted hydantoins, 2. opening of the hydantoin ring to the N-carbamoyl-D-amino acid by D-hydantoinase (E.C.3.5.2.2), 3. converting of the N-carbamoyl-D-amino acid to the D-amino acid by diazotization or by the next enzymatic reaction catalysed by N-carbamylase (E.C.3.5.1.) [5]. D,L-5-substituted hydantoins were obtained as the result of the appropriate aldehydes and hydantoin Knoevenagel condensation, followed by arylidene bond reduction.

[1]Tian, X.; Chen X.; Gan, L.; Hayes, C.J.; Switzer, G.A.; Solinsky, G.M.; Ebetino, H.F.; Wos, A.J.; Pinney, B.B, Farmer, A..J.; Crossdoersen, D.; Sheldon, J.R.; Bioorg. Med. Chem. Lett., 2006, 16, 1721-1725

[2]Peptide Proteins Research Ltd., http://www.peptidesynthetics.co.uk

[3]Reissmann, T.; Schally, A.V.; Bouchard, P.; Riethmiller, H.; Engel, J.; Hum. Repr. Update, 2000, 6 (4), 322-331

[4]Mamoru, W.; Yoshimune, K.; Hirose, Y.; Moriguchi, M.; J. Mol. Cat. B, 2003, 23, 71-85

[5] Wilms, B.; Wiese, A.; Syldatk, C.; Mattes, R.; Altenbuchner, J. J. Biotech, 2001, 86, 19-30

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