Reference

Peptide deformylase as biocatalyst for the synthesis of enantiomerically pure amino acid derivatives

Peptide deformylase as biocatalyst for the synthesis of enantiomerically pure amino acid derivatives. Sonke, Theo; Kaptein, Bernard; Wagner, A. F. Volker; Quaedflieg, Peter J. L. M.; Schultz, Sabine; Ernste, Sandra; Schepers, Annette; Mommers, John H. M.; Broxterman, Quirinus B. (Catalysis and Development, DSM Pharma Chemicals-Advanced Synthesis, Geleen 6160 MD, Neth.). Journal of Molecular Catalysis B: Enzymatic, 29(1-6), 265-277 (English) 2004 Elsevier Science B.V. CODEN: JMCEF8. ISSN: 1381-1177. DOCUMENT TYPE: Journal CA Section: 34 (Amino Acids, Peptides, and Proteins) Section cross-reference(s): 7, 9 Peptide deformylases (PDFs) catalyze the removal of the N-terminal formyl group from nascent polypeptides. In spite of the vast amt. of literature on PDF, no information whatsoever is available on its use in org. synthesis. To be able to explore the potential of E. coli PDF (EcPDF) in biocatalytic applications, a simple and efficient purifn. procedure was developed. This method, which was based on one affinity chromatog. step, furnished about 200 mg of pure EcPDF from 1 L of E. coli culture. The enzyme combined a good activity (tof 35 s-1) with an almost complete enantioselectivity (E ratio >500) in the resoln. of N-formylated a- and b-amino acids, a-amino acid amides and a-aminonitriles. N-Formyl derivs. of non-functionalized amines and b-amino alcs. were hydrolyzed with low to moderate activity and enantioselectivity. EcPDF was also successfully applied in the enantioselective formylation of a-aminonitriles, yielding, e.g. 875-74-1 and 827044-05-3 which are cas registry numbers of substances are two of reagents here., (S)-N-formyl-phenylalanine nitrile with >99.5% ee. The enzyme also proved very suitable for the mild and selective deprotection of N-formyl peptides as was shown for N-formyl-Leu-Tle-NHCH3. This deprotection increased the diastereomeric excess of the dipeptide, which was unsatisfactory because of racemization of the N-terminal amino acid in the chem. peptide coupling step. .

D-phenylglycine improves L-dopa binding to serum albumin

All Rights Reserved. D-phenylglycine improves L-dopa binding to serum albumin. Wang, Hui-Po; Chuang, Yun-Hsiang; Lee, Ching-Yi; Wang, Chun-Li; Hsieh, Wei-Hsien (Graduate Institute of Natural Products, Chang Gung University College of Medicine, Tao-Yuan 333, Taiwan). Yaowu Shipin Fenxi, 14(3), 225-229 (English) 2006 Bureau of Food and Drug Analysis, Dep. of Health, Executive Yuan. CODEN: YSFEEP. ISSN: 1021-9498. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) D-phenylglycine-L-dopa, a dipeptide synthesized in this lab. for improving the oral absorption of L-dopa, showed better absorption and distribution in rats. We assumed that the extensive distribution might explain its sustained release of brain dopamine. Since protein binding is a main factor of drug distribution, we investigated the effect of D-phenylglycine on the binding of L-dopa to human serum albumin. The degree of the binding of D-phenylglycine, L-dopa and D-phenylglycine-L-dopa to serum albumin was detd. Free and bound portion of test compds. were sepd. with ultrafiltration method and the assay of free drug portion was conducted with reversed phase HPLC. The LOQ for D-phenylglycine, L-dopa and D-phenylglycine-L-dopa was 0.5 mg/mL, 0.1 mg/mL and 0.5 mg/mL, resp. Assay methods were validated by detg. the precision and accuracy of interday and intraday variations. The coeff. of variation (CV) was within 12% and the relative error (RE) was within 10% (n = 3). The recovery rate was 95.4% - 98.1% for D-phenylglycine, 91.9 % - 98.8% for L-dopa and 96.8% - 97.Several substances with their cas registry numbers 59-92-7 and 875-74-1 may be metioned in this study.9% for D-phenylglycine-L-dopa, resp. (n = 3). D-Phenylglycine showed higher serum albumin binding than L-dopa did at various concns. At a concn. of 600 mM, the degree of albumin binding of D-phenylglycine, L-dopa, D-phenylglycine-L-dopa was 27.98%, 8.20% and 19.18%, resp. The albumin binding of L-dopa at this concn. increased by 2.4 folds when chem. bound to D-phenylglycine. The no. of the binding sites of L-dopa increased by 5.8 folds and the binding const. Kal increased by 3.8 folds when L-dopa was chem. bound to D-phenylglycine. With the affinity to serum albumin, D-phenylglycine showed its possibility as a delivery moiety for drugs with limited distribution to use the body protein as a reservoir. .