David H. Lee

A synthetic peptide ligase

The preparation of synthetic molecules showing the remarkable efficiencies characteristic of natural biopolymer catalysts remains a formidable challenge for chemical biology. Although significant advances have been made in the understanding of protein structure and function, the de novo construction of such systems remains elusive. Re-engineered natural enzymes and catalytic antibodies, possessing tailored binding pockets with appropriately positioned functional groups, have been successful in catalysing a number of chemical transformations, sometimes with impressive efficiencies. But efforts to produce wholly synthetic catalytic peptides have typically resulted in compounds with questionable structural stability, let alone reactivity. Here we describe a 33-residue synthetic peptide, based on the coiled-coil structural motif, which efficiently catalyses the condensation of two shorter peptide fragments with high sequence- and diastereoselectivity. Depending on the substrates used, we observe rate enhancements of tenfold to 4,100-fold over the background, with catalytic efficiencies in excess of 104. These results augur well for the rational design of functional peptides.

Autocatalytic networks: the transition from molecular self-replication to molecular ecosystems

The transition from inanimate to animate chemistry is thought to involve self-organised networks of molecular species whose collective emergent property gives rise to the overall characteristics of living systems. In the past, simple autocatalytic networks have been constructed that display basic forms of cooperative behaviour. These include reciprocal catalysis, autocratic, and hypercyclic networks. The design and emergent properties of these novel molecular networks are reviewed here.

The oligomeric structure of high molecular weight adiponectin.

There is great interest in the structure of adiponectin as its oligomeric state may specify its biological activities. It occurs as a trimer, a hexamer and a high molecular weight complex. Epidemiological data indicate that the high molecular weight form is significant with low serum levels in type 2 diabetics but to date, has not been well‐defined. To resolve this issue, characterization of this oligomer from bovine serum and 3T3‐L1 adipocytes by sedimentation equilibrium centrifugation and gel electrophoresis respectively, was carried out, revealing that it is octadecameric. Further studies by dynamic light scattering and electron microscopy established that bovine and possibly mouse high molecular weight adiponectin is C1q‐like in structure.

Biologically inspired strategy for programmed assembly of viral building blocks with controlled dimensions.

Facile fabrication of building blocks with precisely controlled dimensions is imperative in the development of functional devices and materials. We demonstrate the assembly of nanoscale viral building blocks of controlled lengths using a biologically motivated strategy. To achieve this we exploit the simple self-assembly mechanism of Tobacco mosaic virus (TMV), whose length is solely governed by the length of its genomic mRNA. We synthesize viral mRNA of desired lengths using simple molecular biology techniques, and in vitro assemble the mRNA with viral coat proteins to yield viral building blocks of controlled lengths. The results indicate that the assembly of the viral building blocks is consistent and reproducible, and can be readily extended to assemble building blocks with genetically modified coat proteins (TMV1cys). Additionally, we confirm the potential utility of the TMV1cys viral building blocks with controlled dimensions via covalent and quantitative conjugation of fluorescent markers. We envision that our biologically inspired assembly strategy to design and construct viral building blocks of controlled dimensions could be employed to fabricate well-controlled nanoarchitectures and hybrid nanomaterials for a wide variety of applications including nanoelectronics and nanocatalysis.

Dynamische Fehlerkorrektur in autokatalytischen Peptid-Netzwerken

Dem Entstehen von Fehlern (der Produktion von mutierten Peptiden) wirkt dieses einfache nichtlineare chemische Netzwerk durch verstarkte Produktion der nativen Sequenz entgegen. Das Netzwerk reagiert auf diese spontan auftretenden Fehler, indem die mutierten Peptide T9A und T26A als Katalysatoren fur die Kondensation der Peptidfragmente E und N, bei der die native selbstreplizierende Sequenz T gebildet wird, herangezogen werden. Dieser Mechanismus der dynamischen Fehlerkorrektur (siehe Bild) konnte fur die Stabilisierung von genomischer Information von Bedeutung sein.

Corrections: Emergence of symbiosis in peptide self-replication through a hypercyclic network

This corrects the article DOI: 10.1038/37569

Unanticipated Trends Stemming from Initial Events in the History of Cell Culture: Vitalism in 2013?

During the period 1907–1912, tissue culture pioneers developed the basic techniques that, with modifications, have been adopted by experimental biologists worldwide to resolve a variety of scientific and technological questions. Because their immediate pragmatic concern was the “growth” of the cells, these pioneers may have inadvertently ignored the theoretical underpinnings of why those cells grew in the artificial conditions they imposed on them. By theoretical underpinnings we mean what premises they adopted to interpret the fact that cells grew outside the organism from where they were explanted, i.e., did they favor proliferation or quiescence as their default state? Here, we argue that the premises adopted and the interpretation of the data they collected introduced important misconceptions that still remain in place. The crucial one has been the notion that quiescence, instead of proliferation, is the default state of cells in metazoan. Later on, this notion led to the claim that there were “signals,” so-called growth factors, that would stimulate those passively quiescent cells to undergo proliferation. Additionally, the notion that quiescence as the default state of cells in metazoa is inimical to evolutionary theory because it implies the intervention of some external, undefined entity that instruct cells to enter their cycle of reproduction. Probably unintentionally, this mistaken conclusion carrying a specific command may be considered as the core of a sort of a naive physicalism that hinders the understanding of biological organization.