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  • 1
    Electronic Resource
    Electronic Resource
    Hamming chromatography (1996)
    Springer
    Molecular diversity 1 (1996), S. 187-192 
    Details
    ISSN: 1573-501X
    Keywords: Random sequences ; Doped libraries ; Selection ; Fitness landscape ; Autocorrelation function ; Hybridization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary Selection of molecules with desired properties from random pools of biopolymers has become a powerful tool in biotechnology. On designing an evolution experiment, a certain knowledge of the concomitant fitness landscape is clearly helpful to set up the optimal experimental conditions. The correlation function is a useful means of characterizing a given landscape, since it can be efficiently measured if one has a method of separating a pool of random sequences according to their Hamming distance from a moderately small number of test sequences. In this paper we describe a special type of hybridization chromatography, where a mixture of oligomers (partially) complementary to a given test sequence is hybridized to the test sequence, covalently bound to a matrix. DNA oligomers are eluted in an ‘effective temperature gradient’ using conditions that minimize the differences of effects of GC versus AT pairs on the melting temperatures. This method should be a means to quickly separate error classes and thus be the crucial step in characterizing fitness landscapes of biopolymers through an experimental approach. It would also be a useful tool to design sequence pools with a bias towards desired mutant spectra.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01544957
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Optimizing doped libraries by using genetic algorithms (1997)
    Springer
    Journal of computer aided molecular design 11 (1997), S. 29-38 
    Details
    ISSN: 1573-4951
    Keywords: Doped libraries ; Molecular evolution ; Protein design ; Codon usage ; Genetic algorithm ; Local optimization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The insertion of random sequences into protein-encoding genes in combination with biologicalselection techniques has become a valuable tool in the design of molecules that have usefuland possibly novel properties. By employing highly effective screening protocols, a functionaland unique structure that had not been anticipated can be distinguished among a hugecollection of inactive molecules that together represent all possible amino acid combinations.This technique is severely limited by its restriction to a library of manageable size. Oneapproach for limiting the size of a mutant library relies on ‘doping schemes’, where subsetsof amino acids are generated that reveal only certain combinations of amino acids in a proteinsequence. Three mononucleotide mixtures for each codon concerned must be designed, suchthat the resulting codons that are assembled during chemical gene synthesis represent thedesired amino acid mixture on the level of the translated protein. In this paper we present adoping algorithm that ‘reverse translates’ a desired mixture of certain amino acids into threemixtures of mononucleotides. The algorithm is designed to optimally bias these mixturestowards the codons of choice. This approach combines a genetic algorithm with localoptimization strategies based on the downhill simplex method. Disparate relativerepresentations of all amino acids (and stop codons) within a target set can be generated.Optional weighing factors are employed to emphasize the frequencies of certain amino acidsand their codon usage, and to compensate for reaction rates of different mononucleotidebuilding blocks (synthons) during chemical DNA synthesis. The effect of statistical errors thataccompany an experimental realization of calculated nucleotide mixtures on the generatedmixtures of amino acids is simulated. These simulations show that the robustness of differentoptima with respect to small deviations from calculated values depends on their concomitantfitness. Furthermore, the calculations probe the fitness landscape locally and allow apreliminary assessment of its structure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008071310472
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  • 3
    Electronic Resource
    Electronic Resource
    Gene assembly based on blunt-ended double-stranded DNA-modules (1998)
    Springer
    Biotechnology techniques 12 (1998), S. 49-54 
    Details
    ISSN: 1573-6784
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Gene synthesis of leucine zipper genes based on blunt end ligation of ds DNA modules was performed in several ligation steps on magnetic beads. A 3'-phosphate, which was removed by T4 polynucleotide kinase after each ligation step, was used to guarantee orientation and single addition of newly added modules. Not depending on sequence complementarity the method appears well suited for the generation of combinatorial libraries of heterologous molecules.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008855526226
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  • 4
    Electronic Resource
    Electronic Resource
    Wissenschaft aktuell (1993)
    Weinheim : Wiley-Blackwell
    Chemie in unserer Zeit 27 (1993), S. 287-293 
    Details
    ISSN: 0009-2851
    Keywords: Chemistry ; Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ciuz.19930270604
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    Paper (German National Licenses)
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  • 5
    Electronic Resource
    Electronic Resource
    mini-chiuz (1992)
    Weinheim : Wiley-Blackwell
    Chemie in unserer Zeit 26 (1992), S. 152-161 
    Details
    ISSN: 0009-2851
    Keywords: Chemistry ; Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ciuz.19920260402
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  • 6
    Electronic Resource
    Electronic Resource
    Growth kinetics of a bacteriophage in continuous culture (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 50 (1996), S. 217-221 
    Details
    ISSN: 0006-3592
    Keywords: Qβ phage ; molecular evolution ; phage display ; continuous culture ; cellstat ; wall growth ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Lytic coliphage Qβ was grown in continuously cultured host bacteria using a cascade of stirred flow reactors. The apparatus was constructed so that the steady stream of exponentially growing bacterial cells passing through the stirred flow reactors served to prevent coevolution brought about by host-parasite interactions. Wall growth was the primary cause for deviation from ideal continuous culture conditions and is largely dependent on the surface structure of the host bacteria. Using an Escherichia coli strain deficient in adhesive type I pili expression, the desynchronization of single burst events could easily be followed over the course of four infection latency periods. Computer simulations based on a two-stage model for the Qβ infection cycle were in perfect agreement with the experimental data. Applications of the optimized system to strategies of molecular evolution are discussed. © 1996 John Wiley & Sons, Inc.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260500204
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    Paper (German National Licenses)
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  • 7
    Electronic Resource
    Electronic Resource
    Molekulare Evolution funktionaler Nukleinsäuren (1999)
    Weinheim : Wiley-Blackwell
    Chemie in unserer Zeit 33 (1999), S. 110-119 
    Details
    ISSN: 0009-2851
    Keywords: Chemistry ; Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: In recent years biologists succeeded in applying strategies of natural evolution to the design of novel compounds. On the basis of large and highly diverse libraries molecules with desired properties are selected. In particular nucleic acids proved to be well suited to adopt a whole variety of functions, including high affinity target binding, specific inhibition of pharmaceutically relevant enzymes, substrate function and various catalytic activities. Altogether, the results brought considerable progress in the field of pharmaceutical drug design as much as they stimulated research on the origin of life. In particular, the theory of an early „RNA world“ preceeding our present DNA-protein-world has since gained a lot of plausibility.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ciuz.19990330207
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