The helicity in water has been determined for several series of alanine-rich peptides that contain single lysine residues and that are N-terminally linked to a helixinducing and reporting template termed Ac-Hel1. The helixpropagating constant for alanine (SAla value) Ac-Hell (Fig. 1C), and these conjugates can be used to distinguish stabilizing effects arising from initiation of a helix from those attributable to its propagation (10-13). As a capping group at the N terminus of a polypeptide, Ac-Hell acts as a helix initiator, and the stability of the helices it initiates within the peptide is proportional to the trans/cis value (t/c) of Ac-Hell, measurable as a ratio of intensities of 'H NMR resonances assigned to s-trans and s-cis conformers of its acetamido function (12, 13). For a particular amino acid residue the helix propagation constant s measures its tendency to join a linked, preexisting helix (14), and for a series of template-linked peptides such as Ac-Hel,-Xn-NH2 or Ac-Hell-Y-Xn-NH2, where Y represents any linking peptide, an average sx can be assigned to amino acids in the X, region from the curvature of a plot of tic vs. n (10, 11, 13). Although one can argue for differences between the helices of this study, propagated unidirectionally in the N-to-C direction, and helices that are propagated from the C terminus or propagated bidirectionally, until evidence to the contrary is forthcoming, it is simpler to view propagation effects measured at a distance from the initiation site as insensitive to the site or nature of the initiation.A lysine residue at the C terminus or in the core of an a-helix may adopt the solvent-exposed conformation shown in Fig. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact. (Fig. 1B). In the latter, lysine may stabilize the helix through a position-dependent electrostatic interaction between the NH3 ion and the helix dipole (9,15,19,20), through a ,r-type hydrogen bond between the NH3 ion and a carbonyl oxygen of the helix core, and through hydrophobic contacts between the hydrocarbon portion of the lysine side chain and the helix core (13,21). If lysine-bearing helices are significantly stabilized by charge-dipole interactions, their helicity is expected to be sensitive to the position of the lysine along the peptide sequence. Moreover, for conformations like that of Fig. 1B, the stabilization attributable to hydrophobic contacts, chargedipole effects, and Tr-hydrogen bonding must change if the length of the lysine side chain is shortened.We have explored this issue in three ways. The tic values for template-peptide conjugates of structure Ac-Hell-Alan-LysAlam-NH2 have been used to assign SAla and to measure the sensitivity of SLys to position. The t/c changes that result when lysine is replaced by amino acid analogs bearing shorter methyleneammonium functions -(CH2)n-NH3, n = 1-3 have been used to pro...

A family of efficient helix-initiating N-terminal caps X-Hel is introduced that expand the scope and versatility of the previously reported reporting conformational template Ac-Hel, (Kemp, D. S.; Allen, T. J.; Oslick, S. J. Am. Chem. Soc. 1995, 117, 6641-6657) and a working principle for predicting cap performance is described, based on structurally specific intramolecular hydrogen bond formation. Replacement of the N-acetyl by urethane, urea, or sulfonamide generated less efficient polypeptide helix inducers. The N-formyl cap is found to be equivalent to the N-acetyl and may provide more convenient quantitative helix reporting properties. Anionic N-caps derived from the series X = (-)O(2)C-(CH(2))(n)-CO, 0 < or = n < or = 3, are superior to N-acetyl, as are N-acylglycyl and N-acyl-beta-aspartyl. The latter pair of caps permit introduction of the X-Hel functionality within a polypeptide chain, allowing control of helicity of a peptide sub-sequence. Applications of these capping functions are discussed. This work has been focused primarily on immediate practical goals directed toward enhancing the maximum helicity of isolated short to medium-sized peptides in aqueous solution, but its developing concepts and working hypotheses are likely to significantly enhance our understanding at a chemical level of the protein folding problem.

Compartment-specific degradation half-lives are essential pieces of information in the regulatory risk assessment of synthetic chemicals. However, their measurement according to regulatory testing guidelines is laborious and costly. Despite the obvious ecological and economic benefits of knowing environmental degradability as early as possible, its consideration in the early phases of rational chemical design is therefore challenging. Here, we explore the possibility to use half-lives determined in highly time-and work-efficient biotransformation experiments with activated sludge and mixtures of chemicals to predict soil half-lives from regulatory simulation studies. We experimentally determined half-lives for 52 structurally diverse agrochemical active ingredients in batch reactors with three concentrations of the same activated sludge. We then developed bi-and multivariate models for predicting half-lives in soil by regressing the experimentally determined half-lives in activated sludge against average soil half-lives of the same chemicals extracted from regulatory data. The models differed in how we accounted for sorption-related bioavailability differences in soil and activated sludge. The best performing models exhibited good coefficients-of-determination (R 2 of around 0.8), low average errors (< factor of 3 in half-life predictions) and were robust in cross-validation. From a practical perspective, these results suggest that it may indeed be possible to read across from half-lives determined in highly efficient biotransformation experiments in activated sludge to soil half-lives, which are obtained from much more work-and resource-intense regulatory studies, and that these predictions are clearly superior to predictions based on the output of the publicly available BIOWIN QSBR model. From a theoretical perspective, these results suggest that soil and activated sludge microbial communities, although certainly different in terms of taxonomic composition, may be functionally similar with respect to the enzymatic transformation of environmentally relevant concentrations of a diverse range of chemical compounds.

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Karrikin (KAR1), also named ‘karrikinolide’, was isolated in 2004 from smoke water and identified as a very potent germination stimulant as well as controlling early seedling development for a large variety of plant species. We reported herein an unprecedented and scalable synthesis of Karrikin (KAR1) based on an elegant and efficient 6‐endo‐dig cyclization. Moreover, we evaluated the effect of KAR1 on corn seeds germination, we carried out additional studies on the uptake of this butenolide into corn seeds, and the main soil chemiodynamic properties (i.e., persistence and mobility) were calculated or estimated. Finally, we provided a rationalization of the experimental results by building a homology model of corn KAI2, using as template the X‐ray of the KAI2 protein from Arabidopsis thaliana.

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Previously we described the utility of the tricyclicdiprolyl structure la as a template for inducing helicity in short iV-terminally linked peptides (cf. lb Figure l).1•2 Peptides of predictable structure find application in medicinal chemistry3 and as models for probing the energetics that underlie the protein folding process. By extending the range of peptides that can exhibit demonstrable helicity, -terminal helical templates potentially provide a means of extending the scope of these applications. Unfortunately, the availability of 1 was limited by our previous synthesis.4 Herein, we report a greatly improved synthesis of lc starting from L-proline and 4-hydroxy-L-proline by a novel tandem intramolecular acyl-transfer-cyclization process.