Triphenylphosphonium Analogs of Short Peptide Related to Bactenecin 7 and Oncocin 112 as Antimicrobial Agents.

Antimicrobial peptides (AMPs) have recently attracted attention as promising antibacterial agents capable of acting against resistant bacterial strains. In this work, an approach was applied, consisting of the conjugation of a peptide related to the sequences of bactenecin 7 (Bac7) and oncocin (Onc112) with the alkyl(triphenyl)phosphonium (alkyl-TPP) fragment in order to improve the properties of the AMP and introduce new ones, expand the spectrum of antimicrobial activity, and reduce the inhibitory effect on the eukaryotic translation process. Triphenylphosphonium (TPP) derivatives of a decapeptide RRIRPRPPYL were synthesized.

Analogs of 6-Bromohypaphorine with Increased Agonist Potency for α7 Nicotinic Receptor as Anti-Inflammatory Analgesic Agents.

Hypaphorines, tryptophan derivatives, have anti-inflammatory activity, but their mechanism of action was largely unknown. Marine alkaloid L-6-bromohypaphorine with EC of 80 μM acts as an agonist of α7 nicotinic acetylcholine receptor (nAChR) involved in anti-inflammatory regulation. We designed the 6-substituted hypaphorine analogs with increased potency using virtual screening of their binding to the α7 nAChR molecular model.

Scope and limitations of pseudoprolines as individual amino acids in peptide synthesis.

Protected 4-carboxyoxazolidines and thiazolidines (pseudoprolines) are derivatives of serine, threonine or cysteine amino acids. Such compounds are used in peptide synthesis among the other protected amino acids. They are usually practiced when a peptide sequence is readily aggregating during synthesis due to their ability to disrupt secondary structure formation.

Spatial Structure and Activity of Synthetic Fragments of Lynx1 and of Nicotinic Receptor Loop C Models.

Lynx1, membrane-bound protein co-localized with the nicotinic acetylcholine receptors (nAChRs) and regulates their function, is a three-finger protein (TFP) made of three β-structural loops, similarly to snake venom α-neurotoxin TFPs. Since the central loop II of α-neurotoxins is involved in binding to nAChRs, we have recently synthesized the fragments of Lynx1 central loop, including those with the disulfide between Cys residues introduced at N- and C-termini, some of them inhibiting muscle-type nAChR similarly to the whole-size water-soluble Lynx1 (ws-Lynx1). Literature shows that the main fragment interacting with TFPs is the C-loop of both nAChRs and acetylcholine binding proteins (AChBPs) while some ligand-binding capacity is preserved by analogs of this loop, for example, by high-affinity peptide HAP.

α9α10 nicotinic acetylcholine receptors regulate murine bone marrow granulocyte functions.

Polymorphonuclear neutrophilic granulocytes (PMNs) are extremely important in defense of the organism against infections and in inflammatory processes including neuroinflammation and pain sensation. Different subtypes of nicotinic acetylcholine receptors (nAChRs) are involved in modulation of PMN activities. Earlier we determined expression of α2-7, α9, β3, β4 subunits and regulatory role of α7 and α3β2 nAChR subtypes in functions of inflammatory PMNs.

Metal-assisted addition of a nitrate anion to bis(oxy)enamines. A general approach to the synthesis of α-nitroxy-oxime derivatives from nitronates.

The synthesis of α-nitroxy-substituted oxime derivatives has been achieved by an unprecedented metal-assisted addition of a nitrate anion to bis(oxy)enamines, which are readily available from nitronates or nitroalkanes. The method has a broad scope and provides access to α-nitroxy-oximes and their cyclic ethers including nitroxy-substituted isoxazolines and dihydro-1,2-oxazines, which are of interest as potential NO-donors and intermediates in the synthesis of bioactive molecules.