Biomedical subjects

J R Granja

Publications and source records attributed to J R Granja.

3 recordsLinked to original sources

PubMed1996

A self-replicating peptide.

The production of amino acids and their condensation to polypeptides under plausibly prebiotic conditions have long been known. But despite the central importance of molecular self-replication in the origin of life, the feasibility of peptide self-replication has not been established experimentally. Here we report an example of a self-replicating peptide. We show that a 32-residue alpha-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-foot of initial template concentration.

Amino Acid Sequence↗

PubMed1994

Artificial transmembrane ion channels from self-assembling peptide nanotubes.

Naturally occurring membrane channels and pores are formed from a large family of diverse proteins, peptides and organic secondary metabolites whose vital biological functions include control of ion flow, signal transduction, molecular transport and production of cellular toxins. But despite the availability of a large amount of biochemical information about these molecules, the design and synthesis of artificial systems that can mimic the biological function of natural compounds remains a formidable task. Here we present a simple strategy for the design of artificial membrane ion channels based on a self-assembled cylindrical beta-sheet peptide architecture. Our systems--essentially stacks of peptide rings--display good channel-mediated ion-transport activity with rates exceeding 10(7) ions s-1, rivalling the performance of many naturally occurring counterparts. Such molecular assemblies should find use in the design of novel cytotoxic agents, membrane transport vehicles and drug-delivery systems.

Amino Acid Sequence↗

PubMed1993

Self-assembling organic nanotubes based on a cyclic peptide architecture.

Hollow tubular structures of molecular dimensions may offer a variety of applications in chemistry, biochemistry and materials science. Concentric carbon nanotubes have attracted a great deal of attention, while the three-dimensional tubular pore structures of molecular sieves have long been exploited industrially. Nanoscale tubes based on organic materials have also been reported previously. Here we report the design, synthesis and characterization of a new class of organic nanotubes based on rationally designed cyclic polypeptides. When protonated, these compounds crystallize into tubular structures hundreds of nanometres long, with internal diameters of 7-8 A. Support for the proposed tubular structures is provided by electron microscopy, electron diffraction, Fourier-transform infrared spectroscopy and molecular modelling. These tubes are open-ended, with uniform shape and internal diameter. We anticipate that they may have possible applications in inclusion chemistry, catalysis, molecular electronics and molecular separation technology.

Amino Acid Sequence↗