Minimalistic ice recrystallisation inhibitors based on phenylalanine.

Ice recrystallisation inhibition (IRI) is typically associated with ice binding proteins, but polymers and other mimetics are emerging. Here we identify phenylalanine as a minimalistic, yet potent, small-molecule IRI capable of inhibiting ice growth at just 1 mg mL. Facial amphiphilicity is shown to be a crucial structural feature, with -substituents enhancing (hydrophobic) or decreasing (hydrophilic) IRI activity.

Ice Recrystallization Inhibition by Amino Acids: The Curious Case of Alpha- and Beta-Alanine.

Extremophiles produce macromolecules which inhibit ice recrystallization, but there is increasing interest in discovering and developing small molecules that can modulate ice growth. Realizing their potential requires an understanding of how these molecules function at the atomistic level. Here, we report the discovery that the amino acid l-α-alanine demonstrates ice recrystallization inhibition (IRI) activity, functioning at 100 mM (∼10 mg/mL).

A semantic sensor web for environmental decision support applications.

Sensing devices are increasingly being deployed to monitor the physical world around us. One class of application for which sensor data is pertinent is environmental decision support systems, e.g.

Synthetic analogues of chymostatin. Inhibition of chymotrypsin and Streptomyces griseus proteinase A.

A series of analogues of chymostatin, including Z-Arg-Leu-Phe-aldehyde (Z-Arg-Leu-Phe-H), have been synthesized. Analysis of the inhibitory potential of these analogues permits identification of residues and interactions that are important for inhibitory activity. Moreover, the structure-function relationship for Z-Arg-Leu-Phe-H and chymostatin inhibition of chymotrypsin and Streptomyces griseus proteinase A (SGPA) was probed further with the aid of molecular mechanics.

Proteinase inhibitors protect Leishmania amazonensis amastigotes from destruction by amino acid esters.

Lysosomotropic amino acid esters and amides kill Leishmania amazonensis amastigotes by a mechanism which probably involves enzymatic hydrolysis of the compounds and rapid accumulation of less permeant amino acid within the parasites. We show here that, in agreement with this model, the proteinase inhibitors antipain and chymostatin prevented the killing of intracellular and isolated parasites by L-leucine methyl ester (Leu-OMe). Survival of Leishmania within macrophages was assessed microscopically, and that of isolated amastigotes was measured by tetrazolium (MTT) reduction.

The effect of analogues of chymostatin on lysosomal and non-lysosomal components of protein degradation in isolated hepatocytes.

Of the proteinase inhibitors derived from Streptomyces spp., chymostatin is the most effective inhibitor of non-lysosomal proteolysis. As part of a systematic study of the structural features of the chymostatin molecule that are responsible for this inhibitory activity, a series of fifteen di- and tripeptide analogues of chymostatin were tested for their ability to suppress protein degradation in isolated primary hepatocytes.

Purple urine bag syndrome.

Purple pigment extracted from the urinary catheters and collecting bags of two elderly female patients was analysed by a variety of chemical techniques, including mass spectroscopy and nuclear magnetic resonance. Although previous studies identified the pigment as indigo, we failed to confirm this. Our analysis also demonstrated that indicanuria is not a requirement for the production of the pigment and furthermore indicates that the molecular structure of the pigment is either a steroidal or bile acid conjugate.

The effect of synthetic analogues of chymostatin upon protein degradation in isolated skeletal muscle.

A series of peptides based on the structure of the proteinase inhibitor chymostatin were tested for their toxicity and ability to suppress protein degradation in the isolated mouse diaphragm. The inhibitory activities of the analogues were very similar, in marked contrast to their disparate abilities as inhibitors of chymotrypsin. Toxicity was determined by measurement of the rates of protein synthesis and of leakage of lactate dehydrogenase into the incubation medium.

Synthetic analogues of the proteinase inhibitor: chymostatin.

Putative proteinase inhibitors with the general structure Z. Arg. X.

Inhibition of hepatic protein degradation by synthetic analogues of chymostatin.

Analogues of the microbial proteinase inhibitor chymostatin have been synthesized. The two most promising analogues were tested on protein turnover in isolated rat hepatocytes. Their effect is much similar to the effect of chymostatin, but the analogues are even more powerful inhibitors, probably due to an increased effect on lysosomal thiol proteinases.

Gel filtration of protected peptides on sephadex G-50 in hexamethylphosphoramide containing 5% water.

Gel permeation chromatography on G-50 and G-75 Sephadex gels, using 5% water in hexamethylphosphoramide (phosphoric trisdimethylamide) has been applied to the purification of large protected peptides which are outside the molecular weight range of the Sephadex LH-20-dimethylformamide system.