Collagen is the most abundant protein in animals. This fibrous, structural protein comprises a righthanded bundle of three parallel, left-handed polyproline II-type helices. Much progress has been made in elucidating the structure of collagen triple helices and the physicochemical basis for their stability. New evidence demonstrates that stereoelectronic effects and preorganization play a key role in that stability. The fibrillar structure of type I collagen-the prototypical collagen fibril-has been revealed in detail. Artificial collagen fibrils that display some properties of natural collagen fibrils are now accessible using chemical synthesis and self-assembly. A rapidly emerging understanding of the mechanical and structural properties of native collagen fibrils will guide further development of artificial collagenous materials for biomedicine and nanotechnology.

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Small-molecule fluorescent probes embody an essential facet of chemical biology. Although numerous compounds are known, the ensemble of fluorescent probes is based on a modest collection of modular "core" dyes. The elaboration of these dyes with diverse chemical moieties is enabling the precise interrogation of biochemical and biological systems. The importance of fluorescence-based technologies in chemical biology elicits a necessity to understand the major classes of small-molecule fluorophores. Here, we examine the chemical and photophysical properties of oft-used fluorophores and highlight classic and contemporary examples in which utility has been built upon these scaffolds.

Lignocellulosic biomass is a plentiful and renewable resource for fuels and chemicals. Despite this potential, nearly all renewable fuels and chemicals are now produced from edible resources, such as starch, sugars, and oils; the challenges imposed by notoriously recalcitrant and heterogeneous lignocellulosic feedstocks have made their production from nonfood biomass inefficient and uneconomical. Here, we report that N,N-dimethylacetamide (DMA) containing lithium chloride (LiCl) is a privileged solvent that enables the synthesis of the renewable platform chemical 5-hydroxymethylfurfural (HMF) in a single step and unprecedented yield from untreated lignocellulosic biomass, as well as from purified cellulose, glucose, and fructose. The conversion of cellulose into HMF is unabated by the presence of other biomass components, such as lignin and protein. Mechanistic analyses reveal that loosely ion-paired halide ions in DMA-LiCl are critical for the remarkable rapidity (1-5 h) and yield (up to 92%) of this low-temperature (

Hydrazones and oximes are common conjugates, but are labile to hydrolysis. The hydrolytic stability of isostructural hydrazones and an oxime have been determined at pD 5.0-9.0. The hydrolysis of each adduct was catalyzed by acid. Rate constants for oxime hydrolysis were nearly 10 3 -fold lower than those for simple hydrazones; a trialkylhydrazonium ion (formed after condensation) was even more stable than the oxime. The data suggest a general mechanism for conjugate hydrolysis. Keywordsconjugates; hydrazones; hydrolysis; oximes; reaction mechanisms Molecules containing carbon-nitrogen double bonds are prevalent in both chemical and biological contexts. The foundations for our current understanding of carbon-nitrogen doublebond formation and hydrolysis were laid by seminal early work on hydrazone hydrolysis and formation,[1] and by contributions from mechanistic studies on enzymes that utilize pyridoxal phosphate.[2] In particular, the meticulous kinetic analyses of Jencks resulted in the delineation of a carbinolamine intermediate in carbon-nitrogen double-bond formation and hydrolysis, and elucidation of the general mechanism of carbonyl-group addition reactions.[3,4] These principles were summarized in a landmark review. [5] Hydrazones and oximes (C 1 =N 1 −X 2 ) possess greater intrinsic hydrolytic stability than do imines. The textbook explanation for this greater stability invokes the participation of X 2 in electron delocalization (Figure 1).[6] The contribution of resonance form II in alkylhydrazones and oximes, and resonance form IV in acylhydrazones increases the negative-charge density

Posttranslational modifications can cause profound changes in protein function. Typically, these modifications are reversible, and thus provide a biochemical on–off switch. In contrast, proline residues are the substrates for an irreversible reaction that is the most common posttranslational modification in humans. This reaction, which is catalyzed by prolyl 4-hydroxylase (P4H), yields (2S,4R)-4-hydroxyproline (Hyp). The protein substrates for P4Hs are diverse. Likewise, the biological consequences of prolyl hydroxylation vary widely, and include altering protein conformation and protein–protein interactions, and enabling further modification. The best known role for Hyp is in stabilizing the collagen triple helix. Hyp is also found in proteins with collagen-like domains, as well as elastin, conotoxins, and argonaute 2. A prolyl hydroxylase domain protein acts on the hypoxia inducible factor α, which plays a key role in sensing molecular oxygen, and could act on inhibitory κB kinase and RNA polymerase II. P4Hs are not unique to animals, being found in plants and microbes as well. Here, we review the enzymic catalysts of prolyl hydroxylation, along with the chemical and biochemical consequences of this subtle but abundant posttranslational modification.

With its wide distribution in soft and hard connective tissues, collagen is the most abundant of animal proteins. In vitro, natural collagen can be formed into highly organized, three-dimensional scaffolds that are intrinsically biocompatible, biodegradable, non-toxic upon exogenous application, and endowed with high tensile strength. These attributes make collagen the material of choice for wound healing and tissue engineering applications. In this article, we review the structure and molecular interactions of collagen in vivo; the recent use of natural collagen in sponges, injectables, films and membranes, dressings, and skin grafts; and the on-going development of synthetic collagen mimetic peptides as pylons to anchor cytoactive agents in wound beds.

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