Peter A V van Hooft

Publications of Peter A V van Hooft

• Evaluation of the antibacterial spectrum of drosocin analogues.

  Authors: Floris J Bikker, Wendy E Kaman-van Zanten, Anne-Marij B C de Vries-van de Ruit, Ingrid Voskamp-Visser, Peter A V van Hooft, Roos H Mars-Groenendijk, Peter C de Visser, Daan Noort

  Chemical biology & drug design. 10/2006; 68(3):148-53.

  Drosocin is a 19-mer, cationic antimicrobial peptide from Drosophila melanogaster. The aim of the study was to examine the antibacterial spectrum of unglycosylated drosocin analogues. Furthermore,Drosocin is a 19-mer, cationic antimicrobial peptide from Drosophila melanogaster. The aim of the study was to examine the antibacterial spectrum of unglycosylated drosocin analogues. Furthermore, the amino acid sequence of DnaK, drosocin's intracellular target, from susceptible species was aligned and studied for sequence homology. From this a panel of 31 bacterial strains, including Salmonella strains with truncated lipopolysaccharide structures, was tested for susceptibility towards three drosocin analogues. Available bacterial DnaK amino acid sequences were retrieved from the ExPASy proteomics server of the Swiss Institute of Bioinformatics studied for sequence homology. Seventeen of the 31 strains tested were susceptible for the drosocin analogues. Minimal inhibitory concentration values against mainly Gram-negative bacteria ranged from 3.1 to 100 microm. With the exception of Micrococcus luteus and Xanthomonas campestris all drosocin analogue-susceptible strains were Enterobacteriaceae showing a high DnaK amino acid sequence homology.

• 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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• Biological evaluation of Tyr6 and Ser7 modified drosocin analogues.

  Authors: Peter C de Visser, Peter A V van Hooft, Anne-Marij de Vries, Ad de Jong, Gijsbert A van der Marel, Herman S Overkleeft, Daan Noort

  Bioorganic & medicinal chemistry letters. 07/2005; 15(11):2902-5.

  An array of analogues of the cationic antimicrobial peptide drosocin was synthesized containing substitutions of Tyr6 and Ser7 in order to increase the proteolytic stability. Stabilizing theAn array of analogues of the cationic antimicrobial peptide drosocin was synthesized containing substitutions of Tyr6 and Ser7 in order to increase the proteolytic stability. Stabilizing the N-terminus with unnatural amino acids increased the serum stability of analogues by almost a factor 30 over an 8 h period.

• Liquid chromatography-mass spectrometry study towards the pH and temperature-induced N-acyl migration in polymyxin B.

  Authors: Peter C de Visser, Cindy Govaerts, Peter A V van Hooft, Herman S Overkleeft, Ann Van Schepdael, Jos Hoogmartens

  Journal of chromatography. A. 12/2004; 1058(1-2):183-9.

  In the course of the synthesis and purification of new polymyxins and analogues, formation of a by-product with identical mass was observed and it was believed that this might be the result of acylIn the course of the synthesis and purification of new polymyxins and analogues, formation of a by-product with identical mass was observed and it was believed that this might be the result of acyl migration from the Nalpha- to the Ngamma-position of residue alpha,-gamma-diaminobutyric acid 1 (Dab1) under acidic conditions. Therefore, a LC-MS/MS study was initiated to establish the stability of polymyxin B3 in aqueous solution at room temperature and 60 degrees C, as well as different pH values (i.e. 1.4, 4.4 and 7.4). It was shown that the by-product, which is actually formed in the course of the purification of polymyxin B3 after evaporation in acidic medium, has a retention time similar to Ngamma-polymyxin B3. Acyl-migration occurred most rapidly at 60 degrees C and pH 7.4. Furthermore, it was established that migration of the acyl from the Nalpha- to the Ngamma-position of residue Dab1 is reversible and that the equilibrium seems to be in favor of the Nalpha-acylated compound.

• A practical synthesis of gramicidin s and sugar amino Acid containing analogues.

  Authors: Gijsbert M Grotenbreg, Martijn Kronemeijer, Mattie S M Timmer, Farid El Oualid, Renate M van Well, Martijn Verdoes, Emile Spalburg, Peter A V van Hooft, Albert J de Neeling, Daan Noort, Jacques H van Boom, Gijsbert A van der Marel, Herman S Overkleeft, Mark Overhand

  The Journal of organic chemistry. 12/2004; 69(23):7851-9.

  A practical gram-scale and high-yielding synthesis of the antimicrobial peptide gramicidin S is presented. An Fmoc-based solid-phase peptide synthesis protocol is employed for the generation of theA practical gram-scale and high-yielding synthesis of the antimicrobial peptide gramicidin S is presented. An Fmoc-based solid-phase peptide synthesis protocol is employed for the generation of the linear decapeptide precursor, which is cyclized in solution to afford the target compound. The versatility of our method is demonstrated by the construction of eight gramicidin S analogues (15a-h) having nonproteinogenic sugar amino acid residues (4-7) incorporated in the turn regions.

• Synthesis and elaboration of functionalised carbohydrate-derived spiroketals.

  Authors: Peter A V van Hooft, Farid El Oualid, Herman S Overkleeft, Gijsbert A van der Marel, Jacques H van Boom, Michiel A Leeuwenburgh

  Organic & biomolecular chemistry. 06/2004; 2(9):1395-403.

  The scope of a stereoselective three-step approach for the synthesis of sugar derived spiroketals is presented. The methodology consists of Grignard addition of vinyl- or allylmagnesium bromide to aThe scope of a stereoselective three-step approach for the synthesis of sugar derived spiroketals is presented. The methodology consists of Grignard addition of vinyl- or allylmagnesium bromide to a carbohydrate lactone, followed by K-10 clay mediated glycosidation with a terminal alkenol and subsequent ring-closing metathesis of the resulting diene. The generality of this procedure is demonstrated by the synthesis of various pyranose- and furanose-derived spiroketals, as well as more advanced tricyclic spiroketal derivatives. It is shown that functionalisation of the double bond in the resulting spiroketals leads to fused polycyclic ethers.