Liquid crystals in biology I. Historical,biological and medical aspects

In our present state of knowledge, it is useful to assume that all matter, in the solar galaxy at least, is composed of atoms and subatomic particles which function independently or interact in accordance with the laws of physics to form molecules, coacervates or other aggregates. For practical purposes, these states of matter are recognizable in the three-dimensional terrestrial world as solids, liquids and gases. This differentiation suffices also for molecular studies but, to understand the properties of mobile organic and especially of living matter fundamentally, it is necessary to investigate and conceptualize how immaterial electromagnetic and electrostatic processes produce changes in state, phase and entropy compatible with self-replication, molecular memory and vitality This possibility exists in the properties of the liquid crystal (LC) as a mesophase in thermal and optical phase transitions, i.e. as an enantiomorphic intermediate form of matter which can form complex, self-replicating, ordered structures and macromolecules, easily recognizable in everyday TV visual displays, electronic communication devices and computers. It is suggested that, in prebiotic terrestrial situations, matter possessing these properties of the LC was a precursor in the evolution of living from inanimate matter and, in the lyotropic form, in the processes of life thereafter.     

Liquid crystals in biology I. Historical, biological and medical aspects

In our present state of knowledge, it is useful to assume that all matter, in the solar galaxy at least, is composed of atoms and subatomic particles which function independently or interact in accordance with the laws of physics to form molecules, coacervates or other aggregates. For practical purposes, these states of matter are recognizable in the three-dimensional terrestrial world as solids, liquids and gases. This differentiation suffices also for molecular studies but, to understand the properties of mobile organic and especially of living matter fundamentally, it is necessary to investigate and conceptualize how immaterial electromagnetic and electrostatic processes produce changes in state, phase and entropy compatible with self-replication, molecular memory and vitality This possibility exists in the properties of the liquid crystal (LC) as a mesophase in thermal and optical phase transitions, i.e. as an enantiomorphic intermediate form of matter which can form complex, self-replicating, ordered structures and macromolecules, easily recognizable in everyday TV visual displays, electronic communication devices and computers. It is suggested that, in prebiotic terrestrial situations, matter possessing these properties of the LC was a precursor in the evolution of living from inanimate matter and, in the lyotropic form, in the processes of life thereafter.     

Natural protective amyloids

Amyloidoses are a group of diseases including neurodegenerative diseases like Alzheimer's disease and also type II diabetes, spongiform encephalopathies and many others, believed to be caused by protein aggregation and subsequent amyloid fibril formation. However, occasionally, living organisms exploit amyloid fibril formation, a property inherent into amino acid sequences, and perform specific physiological functions from amyloids, in differing biological contexts. Some of these functional amyloids are natural protective amyloids. Here, we review recent evidence on silkmoth chorion protein synthetic peptide-analogues that documents the function of silkmoth chorion, the major component of the eggshell, a structure with extraordinary physiological and mechanical properties, as a natural protective amyloid. Also, we briefly discuss the reported function of other natural, protective amyloids like fish chorion, the protein Pmel17 which forms amyloid fibrils that act as templates and accelerate the covalent polymerization of reactive small molecules into melanin, the hydrophobins and the antifreeze protein from winter flounder. Molecular self-assembly is becoming an increasingly popular route to new supramolecular structures and molecular materials and the inspiration for such structures is commonly derived from self-assembling systems in biology. Therefore, a careful examination of these studies may set the basis for the exploration of new routes for the formation of novel biocompatible polymeric structures with exceptional physico-chemical properties, for potentially new biomedical and industrial applications.     

Mineral-organic interfacial processes: potential roles in the origins of life

Life is believed to have originated on Earth ～4.4-3.5 Ga ago, via processes in which organic compounds supplied by the environment self-organized, in some geochemical environmental niches, into systems capable of replication with hereditary mutation. This process is generally supposed to have occurred in an aqueous environment and, likely, in the presence of minerals. Mineral surfaces present rich opportunities for heterogeneous catalysis and concentration which may have significantly altered and directed the process of prebiotic organic complexification leading to life. We review here general concepts in prebiotic mineral-organic interfacial processes, as well as recent advances in the study of mineral surface-organic interactions of potential relevance to understanding the origin of life.     

Semi-Rationally Designed Short Peptides Self-Assemble and Bind Hemin to Promote Cyclopropanation

The self-assembly of short peptides gives rise to versatile nanoassemblies capable of promoting efficient catalysis. We have semi-rationally designed a series of seven-residue peptides that form hemin-binding catalytic amyloids to facilitate enantioselective cyclopropanation with efficiencies that rival those of engineered hemin proteins. These results demonstrate that: 1) Catalytic amyloids can bind complex metallocofactors to promote practically important multisubstrate transformations. 2) Even essentially flat surfaces of amyloid assemblies can impart a substantial degree of enantioselectivity without the need for extensive optimization. 3) The ease of peptide preparation allows for straightforward incorporation of unnatural amino acids and the preparation of peptides made from d -amino acids with complete reversal of enantioselectivity.     

Approaching exponential growth with a self-replicating peptide

Self-replicating peptide systems hold great promise for a wide range of technological applications, as well as to address fundamental questions pertaining to the molecular origins of life. The development of self-replicating compounds capable of high efficiency, however, has remained elusive. Here we disclose a successful strategy whereby modulation of coiled-coil stability results in remarkable catalytic efficiency for self-replication. By shortening the peptide to the minimum length necessary for coiled-coil formation a highly efficient self-replicating system was obtained due to very low background reaction rates, bringing the efficiency close to naturally occurring enzymes.     

Activation chemistry drives the emergence of functionalised protocells

The complexity of the simplest conceivable cell suggests that the chemistry of prebiotic mixtures needs to be explored to understand the intricate network of prebiotic reactions that led to the emergence of life. Early cells probably relied upon compatible and interconnected chemistries to link RNA, peptides and membranes. Here we show that several types of vesicles, composed of prebiotically plausible mixtures of amphiphiles, spontaneously form and sustain the methyl isocyanide-mediated activation of amino acids, peptides and nucleotides. Activation chemistry also drives the advantageous conversion of reactive monoacylglycerol phosphates into inert cyclophospholipids, thus supporting their potential role as major constituents of protocells. Moreover, activation of prebiotic building blocks within fatty acid-based vesicles yields lipidated species capable of localising to and functionalising primitive membranes. Our findings describe a potentially prebiotic scenario in which the components of primitive cells undergo activation and provide new species that might have enabled an increase in the functionality of protocells.

The complexity of the simplest conceivable cell suggests that the chemistry of prebiotic mixtures needs to be explored to understand the intricate network of prebiotic reactions that led to the emergence of life.     

Oligovalent amyloid-binding agents reduce SEVI-mediated enhancement of HIV-1 infection

This paper evaluates the use of oligovalent amyloid-binding molecules as potential agents that can reduce the enhancement of human immunodeficiency virus-1 (HIV-1) infection in cells by semen-derived enhancer of virus infection (SEVI) fibrils. These naturally occurring amyloid fibrils found in semen have been implicated as mediators that can facilitate the attachment and internalization of HIV-1 virions to immune cells. Molecules that are capable of reducing the role of SEVI in HIV-1 infection may, therefore, represent a novel strategy to reduce the rate of sexual transmission of HIV-1 in humans. Here, we evaluated a set of synthetic, oligovalent derivatives of benzothiazole aniline (BTA, a known amyloid-binding molecule) for their capability to bind cooperatively to aggregated amyloid peptides and to neutralize the effects of SEVI in HIV-1 infection. We demonstrate that these BTA derivatives exhibit a general trend of increased binding to aggregated amyloids as a function of increasing valence number of the oligomer. Importantly, we find that oligomers of BTA show improved capability to reduce SEVI-mediated infection of HIV-1 in cells compared to a BTA monomer, with the pentamer exhibiting a 65-fold improvement in efficacy compared to a previously reported monomeric BTA derivative. These results, thus, support the use of amyloid-targeting molecules as potential supplements for microbicides to curb the spread of HIV-1 through sexual contact.     

Peptide bond formation in gas-phase ion/molecule reactions of amino acids: a novel proposal for the synthesis of prebiotic oligopeptides

There is a general fascination with regard to the origin of life on Earth. There is an intriguing possibility that prebiotic precursors of life occurred in the interstellar space and were then transported to the early Earth by comets, asteroids and meteorites. It is probable that some part of the prebiotic molecules may have been generated by gas-phase ion/molecule reactions. Here we show experimentally that gaseous ion/molecule reactions of the amino acids, Glu and Met, may promote the synthesis of protonated dipeptides such as (Glu-Glu)H(+) and (Glu-Met)H(+) and their chemical growth to larger protonated peptides.     

Plasma Modeling and Prebiotic Chemistry: A Review of the State-of-the-Art and Perspectives

We review the recent progress in the modeling of plasmas or ionized gases, with compositions compatible with that of primordial atmospheres. The plasma kinetics involves elementary processes by which free electrons ultimately activate weakly reactive molecules, such as carbon dioxide or methane, thereby potentially starting prebiotic reaction chains. These processes include electron–molecule reactions and energy exchanges between molecules. They are basic processes, for example, in the famous Miller-Urey experiment, and become relevant in any prebiotic scenario where the primordial atmosphere is significantly ionized by electrical activity, photoionization or meteor phenomena. The kinetics of plasma displays remarkable complexity due to the non-equilibrium features of the energy distributions involved. In particular, we argue that two concepts developed by the plasma modeling community, the electron velocity distribution function and the vibrational distribution function, may unlock much new information and provide insight into prebiotic processes initiated by electron–molecule collisions.     

Ubiquitous Amyloids

The common view of amyloids and prion proteins is that they are associated with many currently incurable diseases and present a great danger to an organism. This danger comes from the fact that not only prion proteins, but also the infectious form(s) of amyloids, as it has been shown recently, are able to transmit the disease. On the other hand, organisms take advantage of the strength and durability of specific forms of amyloids. Such forms do not spread any disease. Also, in nanotechnology there is a constantly growing need to employ amyloid fibrils in many industrial applications. With increasing knowledge about amyloids and prion proteins we are aware that the amyloidal state is inherent to any protein, making the problem of amyloid formation a central one in aging-related diseases. However, the “good” amyloids can be beneficial and even necessary for our health. Furthermore, because of their mechanical properties, the amyloids are of great interest to engineers.     

Probing structural effects on replication efficiency through comparative analyses of families of potential self-replicators

A formidable synthetic apparatus for the creation of nanoscale molecular structures and supramolecular assemblies through molecular structures can potentially be created from systems that are capable of parallel automultiplication (self-replication). In order to achieve this goal, a detailed understanding of the relationship between molecular structure and replication efficiency is necessary. Diastereoisomeric templates that are capable of specific and simultaneous autocatalysis have been synthesised. A systematic experimental and theoretical evaluation of their behaviour and that of structurally-related systems reveals the key determinants that dictate the emergence of self-replicative function and defines the structural space within which this behaviour is observed.     

Semi‐Rationally Designed Short Peptides Self‐Assemble and Bind Hemin to Promote Cyclopropanation

The self‐assembly of short peptides gives rise to versatile nanoassemblies capable of promoting efficient catalysis. We have semi‐rationally designed a series of seven‐residue peptides that form hemin‐binding catalytic amyloids to facilitate enantioselective cyclopropanation with efficiencies that rival those of engineered hemin proteins. These results demonstrate that: 1) Catalytic amyloids can bind complex metallocofactors to promote practically important multisubstrate transformations. 2) Even essentially flat surfaces of amyloid assemblies can impart a substantial degree of enantioselectivity without the need for extensive optimization. 3) The ease of peptide preparation allows for straightforward incorporation of unnatural amino acids and the preparation of peptides made from d ‐amino acids with complete reversal of enantioselectivity.     

A Stark Contrast to Modern Earth: Phosphate Mineral Transformation and Nucleoside Phosphorylation in an Iron‐ and Cyanide‐Rich Early Earth Scenario

Organophosphates were likely an important class of prebiotic molecules. However, their presence on the early Earth is strongly debated because the low availability of phosphate, which is generally assumed to have been sequestered in insoluble calcium and iron minerals, is widely viewed as a major barrier to organophosphate generation. Herein, we demonstrate that cyanide (an essential prebiotic precursor) and urea‐based solvents could promote nucleoside phosphorylation by transforming insoluble phosphate minerals in a “warm little pond” scenario into more soluble and reactive species. Our results suggest that cyanide and its derivatives (metal cyanide complexes, urea, ammonium formate, and formamide) were key reagents for the participation of phosphorus in chemical evolution. These results allow us to propose a holistic scenario in which an evaporitic environment could concentrate abiotically formed organics and transform the underlying minerals, allowing significant organic phosphorylation under plausible prebiotic conditions.     

Synthesis of Prebiotic Building Blocks by Photochemistry

Ultraviolet(UV) light is a very competent energy source for the synthesis of prebiotic building blocks on early Earth. In aqueous solution, hydrated electron is produced by irradiating ferrocyanide/cuprous cyanide/hydrosulfide by 254 nm UV light. Hydrated electron is a powerful reducing reagent driving the formation of prebiotic building blocks under prebiotically plausible conditions. Here we summarize the photoredox synthesis of prebiotic related building blocks from hydrogen cyanide(HCN) and other prebiotically related molecules. These results indicate biological related building blocks can be generated on the surface of early Earth.     

Prebiotically Plausible Organocatalysts Enabling a Selective Photoredox α-Alkylation of Aldehydes on the Early Earth

Organocatalysis is a powerful approach to extend and (enantio-) selectively modify molecular structures. Adapting this concept to the Early Earth scenario offers a promising solution to explain their evolution into a complex homochiral world. Herein, we present a class of imidazolidine-4-thione organocatalysts, easily accessible from simple molecules available on an Early Earth under highly plausible prebiotic reaction conditions. These imidazolidine-4-thiones are readily formed from mixtures of aldehydes or ketones in presence of ammonia, cyanides and hydrogen sulfide in high selectivity and distinct preference for individual compounds of the resulting catalyst library. These organocatalysts enable the enantioselective α-alkylation of aldehydes under prebiotic conditions and show activities that correlate with the selectivity of their formation. Furthermore, the crystallization of single catalysts as conglomerates opens the pathway for symmetry breaking.     

Comparative analyses of a family of potential self-replicators: the subtle interplay between molecular structure and the efficacy of self-replication

It is envisioned that protocols based on self-replication will emerge as a formidable synthetic apparatus for the production of nanoscale assemblies through molecular structures that are capable of automultiplication with high reaction rates and selectivities. To achieve this goal, a complete understanding of the relationship between molecular structure and replication efficiency is necessary. Rigorous experimental and theoretical analyses of a series of self-complementary scaffolds that are intimately related in a constitutional sense, manufactured through the Diels-Alder reaction of complementary subunits, were undertaken. Experimental and computational methods were employed to map the key determinants that dictate the emergence of self-replicative function, as well as the efficiency, rate and selectivity of the self-replicative processes.     

Plausible Emergence of Biochemistry in Enceladus Based on Chemobrionics

Saturn's satellite Enceladus is proposed to have a soda-type subsurface ocean with temperature able to support life and an iron ore-based core. Here, it was demonstrated that ocean chemistry related to Enceladus can support the development of Fe-based hydrothermal vents, one of the places suggested to be the cradle of life. The Fe-based chemical gardens were characterized with Fourier-transform (FT)IR spectroscopy and XRD. The developed chemobrionic structures catalyzed the condensation polymerization of simple organic prebiotic molecules to kerogens. Further, they could passively catalyze the condensation of the prebiotic molecule formamide to larger polymers, suggesting that elementary biochemical precursors could have emerged in Enceladus.     

Dynamic combinatorial libraries: new opportunities in systems chemistry

Combinatorial chemistry is a tool for selecting molecules with special properties. Dynamic combinatorial chemistry started off aiming to be just that. However, unlike ordinary combinatorial chemistry, the interconnectedness of dynamic libraries gives them an extra dimension. An understanding of these molecular networks at systems level is essential for their use as a selection tool and creates exciting new opportunities in systems chemistry. In this feature article we discuss selected examples and considerations related to the advanced exploitation of dynamic combinatorial libraries for their originally conceived purpose of identifying strong binding interactions. Also reviewed are examples illustrating a trend towards increasing complexity in terms of network behaviour and reversible chemistry. Finally, new applications of dynamic combinatorial chemistry in self-assembly, transport and self-replication are discussed.     

Complementary nucleobase interaction enhances peptide-peptide recognition and self-replicating catalysis

The availability of the complementary interaction of nucleobases for influencing the formation of peptide architectures was explored. Nucleobases were incorporated as additional recognition elements in coiled-coil peptides by employing nucleobase amino acids (NBAs), which are artificial L-alpha-amino gamma-nucleobase-butyric acids. The effect of the base-pair interaction on intermolecular recognition between peptides was evaluated through a self-replication reaction. The self-replication reactions of the peptides with complementary base pairs such as thymine-adenine or guanine-cytosine at the g-g' heptad positions were accelerated in comparison with those of the peptides with mismatched base pairs or without nucleobases. However, thymine-adenine pairs at the e-e' positions did not enhance the self-replication. In the presence of a denaturant, the enhancement effects of complementary base pairs on the reaction disappeared. Thermal denaturation studies showed that the thymine-adenine pairs contributed to stabilization of the coiled-coil structure and that the pairs at the g-g' positions were more effective than those at the e-e' positions. The peptide-peptide interaction was reinforced by complementary nucleobase interactions appropriately arranged in the peptide structure; these led to acceleration of the self-replication reactions.