论文信息 - Directed evolution of trypsin inhibiting peptides using a genetic algorithm

Directed evolution of trypsin inhibiting peptides using a genetic algorithm

A new strategy which employs a process of directed evolution in the search for molecules exhibiting certain desirable properties is reported. By repeating a cycle of peptide synthesis, evaluation of the trypsin inhibitory activities of these peptides and subsequent selection and transformation based on a genetic algorithm, it is possible artificially to induce the evolution of a family of peptides and improve their biological activities. Commencing with a set of 24 randomly generated hexapeptides, a progressive improvement from 16 to 50% average inhibitory activity over six generations, with maximum activities of 80–90% is observed. The emergence of consensus sequences which concur with those previously generated using peptide libraries is also observed.

[1] W. Stemmer. Rapid evolution of a protein in vitro by DNA shuffling , 1994, Nature.

[2] R. Houghten,et al. Generation and use of synthetic peptide combinatorial libraries for basic research and drug discovery , 1991, Nature.

[3] W. C. Still,et al. Peptidosteroidal Receptors for Opioid Peptides. Sequence-Selective Binding Using a Synthetic Receptor Library , 1994 .

[4] S Forrest,et al. Genetic algorithms , 1996, CSUR.

[5] Klaus Gubernator,et al. Optimization of the Biological Activity of Combinatorial Compound Libraries by a Genetic Algorithm , 1995 .

[6] K. Lam,et al. A new type of synthetic peptide library for identifying ligand-binding activity , 1992, Nature.

[7] Edward P. Jaeger,et al. Application of Genetic Algorithms to Combinatorial Synthesis: A Computational Approach to Lead Identification and Lead Optimization†,∇ , 1996 .

[8] J. Bermak,et al. A Transition State Analog Inhibitor Combinatorial Library , 1995 .

[9] W. C. Still,et al. SEQUENCE-SELECTIVE PEPTIDE BINDING WITH A PEPTIDO-A,B-TRANS-STEROIDAL RECEPTOR SELECTED FROM AN ENCODED COMBINATORIAL RECEPTOR LIBRARY , 1996 .