Chemoproteomic Evaluation of the Polyacetylene Callyspongynic Acid

Polyacetylenes are a class of alkyne‐containing natural products. Although potent bioactivities and thus possible applications as chemical probes have already been reported for some polyacetylenes, insights into the biological activities or molecular mode of action are still rather limited in most cases. To overcome this limitation, we describe the application of the polyacetylene callyspongynic acid in the development of an experimental roadmap for characterizing potential protein targets of alkyne‐containing natural products. To this end, we undertook the first chemical synthesis of callyspongynic acid. We then used in situ chemical proteomics methods to demonstrate extensive callyspongynic acid‐mediated chemical tagging of endoplasmic reticulum‐associated lipid‐metabolizing and modifying enzymes. We anticipate that an elucidation of protein targets of natural products may serve as an effective guide to the development of subsequent biological assays that aim to identify chemical phenotypes and bioactivities.     

Formation and Stability of Binary Complexes of Divalent Ecotoxic Ions (Ni, Cu, Zn, Cd, Pb) with Biodegradable Aminopolycarboxylate Chelants (dl-2-(2-Carboxymethyl)Nitrilotriacetic Acid, GLDA, and 3-Hydroxy-2,2′-Iminodisuccinic Acid, HIDS) in Aqueous Solutions

The protonation and complex formation equilibria of two biodegradable aminopolycarboxylate chelants {dl-2-(2-carboxymethyl)nitrilotriacetic acid (GLDA) and 3-hydroxy-2,2??-iminodisuccinic acid (HIDS)} with Ni²⁺, Cu²⁺, Zn²⁺, Cd²⁺ and Pb²⁺ ions were investigated using the potentiometric method at a constant ionic strength of I?=?0.10?mol·dm^?3 (KCl) in aqueous solutions at 25?±?0.1?°C. The stability constants of the proton?Cchelant and metal?Cchelant species for each metal ion were determined, and the concentration distributions of various complex species in solution were evaluated for each ion. The stability constants (log₁₀ K _ML) of the complexes containing Ni²⁺, Cu²⁺, Zn²⁺, Cd²⁺ and Pb²⁺ ions followed the identical order of log₁₀ K _CuL?>?log₁₀ K _NiL?>?log₁₀ K _PbL?>?log₁₀ K _ZnL?>?log₁₀ K _CdL for either GLDA (13.03?>?12.74?>?11.60?>?11.52?>?10.31) or HIDS (12.63?>?11.30?>?10.21?>?9.76?>?7.58). In each case, the constants obtained for metal?CGLDA complexes were larger than the corresponding constants for metal?CHIDS complexes. The conditional stability constants (log₁₀ $ K_{\text{ML}}^{'} $ ) of the metal?Cchelant complexes containing GLDA and HIDS were calculated in terms of pH, and compared with the stability constants for EDTA and other biodegradable chelants.     

On relative stability of linear stationary feedback control systems with time delay

A method is presented whereby the absolute and relative stabilityof linear control systems containing transport lag can be determined.As a result feedback systems with variable time delay and loopgain, may be investigated in straightforward manner.