Annelies E M Buizert

Publications of Annelies E M Buizert

• Beta-turn modified gramicidin S analogues containing arylated sugar amino acids display antimicrobial and hemolytic activity comparable to the natural product.

  Authors: Gijsbert M Grotenbreg, Annelies E M Buizert, Antonio L Llamas-Saiz, Emile Spalburg, Peter A V van Hooft, Albert J de Neeling, Daan Noort, Mark J van Raaij, Gijsbert A van der Marel, Herman S Overkleeft, Mark Overhand

  Journal of the American Chemical Society. 07/2006; 128(23):7559-65.

  This paper describes the design and synthesis of gramicidin S (GS) analogues 10a-c containing arylated sugar amino acids (SAAs) as a replacement of one of the two (D)Phe-Pro beta-turn regions. TheThis paper describes the design and synthesis of gramicidin S (GS) analogues 10a-c containing arylated sugar amino acids (SAAs) as a replacement of one of the two (D)Phe-Pro beta-turn regions. The cyclic, amphiphilic peptides adopt a beta-sheet conformation featuring an unusual reverse turn induced by the SAAs. The altered turn region induces a slight distortion of the antiparallel beta-sheet, as compared to GS; the overall geometry however closely resembles that of the nonarylated GS analogue 1. GS analogues 10a-c proved to be as active as the parent GS itself as antibacterial agents and are equally efficient in lysing red blood cells. These properties are in sharp contrast to the diminished biological activity displayed by 1. We conclude that the presence of aromaticity in the turn regions of GS derivatives is required for biological activity, whereas the native conformation of the beta-hairpin is not. Our findings may guide future research toward efficient and nonhemolytic GS analogues for combating bacterial infections.

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• Synthesis and application of carbohydrate-derived morpholine amino acids.

  Authors: Gijsbert M Grotenbreg, Alphert E Christina, Annelies E M Buizert, Gijsbert A van der Marel, Herman S Overkleeft, Mark Overhand

  The Journal of organic chemistry. 12/2004; 69(24):8331-9.

  The synthesis of series of diversely functionalized epsilon-morpholine amino acids (MAAs, 5a-h) starting from an epsilon-sugar amino acid and following a two-step oxidative glycol cleavage/reductiveThe synthesis of series of diversely functionalized epsilon-morpholine amino acids (MAAs, 5a-h) starting from an epsilon-sugar amino acid and following a two-step oxidative glycol cleavage/reductive amination strategy, is described. In an alternative synthetic scheme, diastereoisomerically pure delta-MAAs (12a,b) were obtained. Oligopeptides containing MAAs were prepared either by direct incorporation of a MAA building block or by subjecting a fully assembled SAA-containing peptide to the two-step glycol cleavage/reductive amination procedure.