A self-replicating peptide

THE production of amino acids and their condensation to polypeptides under plausibly prebiotic conditions have long been known1,2. But despite the central importance of molecular self-replication in the origin of life, the feasibility of peptide self-replication has not been established experimentally3–6. Here we report an example of a self-replicating peptide. We show that a 32-residue α-helical peptide based on the leucine-zipper domain of the yeast transcription factor GCN4 can act autocatalytically in templating its own synthesis by accelerating the thioester-promoted amide-bond condensation of 15- and 17-residue fragments in neutral, dilute aqueous solutions. The self-replication process displays parabolic growth pattern with the initial rates of product formation correlating with the square-root of initial template concentration.

[1]  M. Matzen,et al.  Parabolic Growth of a Self‐Replicating Hexadeoxynucleotide Bearing a 3'‐5'‐Phosphoamidate Linkage , 1991 .

[2]  Juan R. Granja,et al.  Self-assembling organic nanotubes based on a cyclic peptide architecture , 1993, Nature.

[3]  S. Pitsch,et al.  PYRANOSYL-RNA ('P-RNA') : BASE-PAIRING SELECTIVITY AND POTENTIAL TO REPLICATE , 1995 .

[4]  S. Fox,et al.  Molecular evolution and the origin of life , 1972 .

[5]  R. Hodges,et al.  Synthetic model proteins: the relative contribution of leucine residues at the nonequivalent positions of the 3-4 hydrophobic repeat to the stability of the two-stranded alpha-helical coiled-coil. , 1992, Biochemistry.

[6]  Kenji Kobayashi,et al.  β-Sheet Peptide Architecture: Measuring the Relative Stability of Parallel vs. Antiparallel β-Sheets†‡ , 1995 .

[7]  E. Wintner,et al.  Self-Replicating Molecules: A Second Generation , 1994 .

[8]  D. Sievers,et al.  Self-replication of complementary nucleotide-based oligomers , 1994, Nature.

[9]  E. Wintner,et al.  Evidence against an Alternative Mechanism for a Self-Replicating System , 1995 .

[10]  P. S. Kim,et al.  A switch between two-, three-, and four-stranded coiled coils in GCN4 leucine zipper mutants. , 1993, Science.

[11]  Günter von Kiedrowski,et al.  A Self‐Replicating Hexadeoxynucleotide , 1986 .

[12]  D Eisenberg,et al.  3D domain swapping: A mechanism for oligomer assembly , 1995, Protein science : a publication of the Protein Society.

[13]  L. Orgel,et al.  Autocatalytic synthesis of a tetranucleotide analogue , 1987, Nature.

[14]  G. Kiedrowski,et al.  Sequence Dependence of Template‐Directed Syntheses of Hexadeoxynucleotide Derivatives with 3′–5′ Pyrophosphate Linkage , 1989 .

[15]  Julius Rebek,et al.  Self-replicating system , 1990 .

[16]  James C. Hu,et al.  Sequence requirements for coiled-coils: analysis with lambda repressor-GCN4 leucine zipper fusions. , 1990, Science.

[17]  L. Orgel.  The Origins of Life on the Earth , 1974 .

[18]  K. Nicolaou,et al.  Chemical self-replication of palindromic duplex DNA , 1994, Nature.

[19]  Günter von Kiedrowski,et al.  Minimal Replicator Theory I: Parabolic Versus Exponential Growth , 1993 .

[20]  Julius Rebek,et al.  Kinetic studies and modeling of a self-replicating system , 1991 .

[21]  S. Kauffman.  Autocatalytic sets of proteins. , 1986 .