Novel mastoparan analogs induce differential secretion from mast cells

Cationic amphiphilic peptides stimulate secretion via a receptor-independent action upon G proteins. We have previously utilized chimeric analogs of mastoparan (MP), including galparan (galanin(1-13)-MP ), as molecular probes of secretion. Here, we further resolve the structure-activity relationship of peptidyl secretagogs, including rationally designed chimeric MP analogs. The secretory efficacies of 10 MP analogs were significantly higher than 45 unrelated basic peptides. Comparative studies identified MP analogs that are differential secretagogs for 5-hydroxytryptamine (5-HT) and beta-hexosaminidase. Peptide-induced activation of phospholipase D (PLD), an enzyme intimately involved in regulated exocytosis [5], correlated with the secretion of beta-hexosaminidase but not 5-HT. Thus, these data indicate that different mechanisms are responsible for the exocytosis of 5-HT and beta-hexosaminidase, respectively. Moreover, mastoparan analogs are novel tools for probing the molecular details of exocytosis and other biological phenomena.     

Synthesis of analogs of natural isoflavones from 2,4-dihydroxydeoxybenzoins

A number of analogs of natural isoflavones have been synthesized. The starting materials were 2,4-dihydroxydeoxybenzoins obtained under modified conditions of the Houben-Hoesch reaction. The yields of the isoflavones synthesized were 63–69%. All the analogs of natural flavones possess a pronounced hypolipidemic action.     

Bacteriorhodopsin analogs from diphenylpolyene chromophores

Chromophore-modified bacteriorhodopsin (bR) analogs are prepared, to study the nature of chromophore-protein interaction as well as to develop new bR analogs that can find applications as photoactive element in molecular electronic devices. This article describes the preparation and characterization of hitherto unknown bR analogs based on diphenylpolyene chromophores. Diphenylpolyene compounds, namely, 4-[(E)-2-phenylvinyl]benzaldehyde (1), 3-methyl-5-[4-[(E)-2-phenylvinyl]phenyl]penta-2E,4E-dienal (2), 4-[4-phenylbuta-1E,3E-dienyl]benzaldehyde (3) and 3-methyl-5-[4-[4-phenylbuta-lE,3E-dienyl]phenyl]penta-2E,4E-dienal (4), have been synthesized, and their interaction with bacterioopsin (bOP) has been studied. Whereas aldehydes 2 and 4 interact with bOP and yield bR analogs bR-2 and bR-4, aldehydes 1 and 3 do not yield any pigment. Analogs bR-2 and bR-4 have been characterized for their opsin shift, competitive binding, photochemical properties and fluorescence spectral behavior.     

Preparation and separation of antimicrobial agents derived from capreomycin

A practical method for the preparation of single component biaryl-urea analogs of capreomycin is described. The protocol involves derivatization of capreomycin followed by global protection of the capreomycin analog mixture. The individual components were separated using simple flash column chromatography followed by deprotection to give the desired analogs with high purity.     

Study on the Interaction between Distamycin Analogs and DNA from Herring Sperm by Fluorimetry

Distamycin is a naturally occurring antibiotic which binds to the AT rich regions in minor groove of DNA1. We have reported the interaction between the analogs and calf thymus DNA by circular dichroism spectropolarimetry (CD) and isothermal titration calorimetry (ITC)2. Due to the greater sensitivity of fluorescence-based techniques in comparison with CD, we employ the fluorimety to explore the interaction between four new distamycin analogs and DNA from herring sperm. O2NNNOHNNO…     

Room Temperature Phosphorescence from Tryptophan and Halogenated Tryptophan Analogs in Amorphous Sucrose

Abstract. Tryptophan phosphorescence lifetime and quantum yield are sensitive to the local environment. The phosphorescence from tryptophan analogs, however, has not been studied. We report here data on the room temperature phosphorescence of tryptophan, 4-, 5- and 6-fluoro-DL-tryptophan (4-F-trp, 5-F-trp and 6-F-trp) and 5-bromo-DL-tryptophan (5-Br-trp) embedded in glassy powders of freeze-dried sucrose. In aqueous solution, the absorption of the analogs was either blue-shifted (4-F-trp), red-shifted (5-F-trp and 5-Br-trp) or not shifted (6-F-trp) with respect to tryptophan. The phosphorescence emission spectra of all analogs were red-shifted compared to trp (442 nm) with maxima at 446 nm (5-F-trp), 451 mn (6-F-trp), 452 nm (5-Br-trp) and 469 nm (4-F-trp). The 5-F-trp and 6-F-trp analogs had emission intensities similar to tryptophan (relative quantum yields of 0.68 and 0.91, respectively, compared to tryptophan), while the intensities of the 4-F and 5-Br analogs were lower (relative quantum yields of 0.039 and 0.022, respectively). All analogs exhibited complex decay behavior requiring several exponentials for an adequate fit; the average lifetimes were all lower than that of trp (1039 ms). The average lifetimes of the fluorinated analogs (5-F, 721 ms; 6-F, 482 ms and 4-F, 35 ms) scaled approximately with the relative quantum yields while that of 5-Br (0.53 ms) was significantly lower. Analysis of the individual lifetimes suggested that the fluorinated analogs differ in their sensitivity to environmental interactions, with 5-F- and 6-F-trp quenched 1.5-2-fold and 4-F-trp about 23-fold more efficiently than tryptophan. The red-shifted 5-F-trypto-phan analog, which has been incorporated into proteins, may provide an alternative phosphorescence probe for selective phosphorescence detection of a specific protein in a complex mixture.     

Synthesis of analogs of natural isoflavones from 2,4-dihydroxydeoxybenzoins

A number of analogs of natural isoflavones have been synthesized. The starting materials were 2,4-dihydroxydeoxybenzoins obtained under modified conditions of the Houben-Hoesch reaction. The yields of the isoflavones synthesized were 63–69%. All the analogs of natural flavones possess a pronounced hypolipidemic action.Pyatigorsk Pharmaceutical Institute. Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 781–784, November–December, 1985.     

First natural analogs of the cytotoxic thiodepsipeptide thiocoraline A from a marine Verrucosispora sp

A marine Verrucosispora sp. isolated from the sponge Chondrilla caribensis f. caribensis was found to produce thiocoraline, a potent cytotoxic compound. Five new analogs of thiocoraline were isolated and represent the first analogs of thiocoraline. 22'-Deoxythiocoraline (2), thiochondrilline C (5), and 12'-sulfoxythiocoraline (6) demonstrated significant cytotoxicity against the A549 human cancer cell line with EC(50) values of 0.13, 2.86, and 1.26 μM, respectively. The analogs provide insight into the SAR and biosynthesis of thiocoraline. The DP4 probability method was used to analyze ab initio NMR calculations to confirm stereochemical assignments.     

Nature of reissert analogs derived from N,N-dialkyl and N,N-diaryl carbamoyl chlorides

Reissert analogs were prepared from the reaction of isoquinoline and phthalazine with carbamoyl chlorides and cyanide using the methylene chloride-water method. Alkylation, condensation, Michael addition, and hydrolysis reactions of these Reissert analogs have been studied and found in many cases, to be similar to those of the isoquinoline Reissert compound.     

Structure–activity relationship of novel juvenile hormone,JHSB3, isolated from the stink bug,Plautia stali

The structure–activity relationship of JHSB₃ isolated from the pentatomid bug, Plautia stali, was studied. Various synthetic analogs were synthesized and subjected to the juvenilizing activity tests using the last instar nymphs of P. stali. These studies indicated that the coexistence of the ester carbonyl group, two epoxides at C2,3 and C10,11 were proved to be crucial for the potent juvenilizing activity. Among the tested analogs, we found highly potent analogs in which the C6,7 double bond of JHSB₃ was saturated (0.1 μg/insect). The methoxy analogs in which the epoxide moiety at C10,11 was substituted with a methoxy group exerted a moderate juvenilizing activity.     

Synthesis of aryl-containing isoprenoids from 1,5-dimethylcycloocta-1,5-diene

A procedure has been developed for the synthesis of Pro-Drone homo analogs from the ozonolysis products of 1,5-dimethylcycloocta-1,5-diene and 1,5-dimethylcyclooctene.     

Engineering strategy to improve peptide analogs: from structure-based computational design to tumor homing

We present a chemical strategy to engineer analogs of the tumor-homing peptide CREKA (Cys-Arg-Glu-Lys-Ala), which binds to fibrin and fibrin-associated clotted plasma proteins in tumor vessels (Simberg et al. in Proc Natl Acad Sci USA 104:932–936, 2007) with improved ability to inhibit tumor growth. Computer modeling using a combination of simulated annealing and molecular dynamics were carried out to design targeted replacements aimed at enhancing the stability of the bioactive conformation of CREKA. Because this conformation presents a pocket-like shape with the charged groups of Arg, Glu and Lys pointing outward, non-proteinogenic amino acids α-methyl and N-methyl derivatives of Arg, Glu and Lys were selected, rationally designed and incorporated into CREKA analogs. The stabilization of the bioactive conformation predicted by the modeling for the different CREKA analogs matched the tumor fluorescence results, with tumor accumulation increasing with stabilization. Here we report the modeling, synthetic procedures, and new biological assays used to test the efficacy and utility of the analogs. Combined, our results show how studies based on multi-disciplinary collaboration can converge and lead to useful biomedical advances.     

Antagonists of substance P from emphasis on position 11

Ten analogs of substance P (SP) were designed and synthesized. The agonist and antagonist activities against SP were assayed on the isolated guinea pig ileum. The prime designs were changes of the important Met11 to include Leu11, Thr11, D-Leu11 and D-Ala11. Step-wise designs of changing D-Arg1 and D-Pro2 to the corresponding L-configurations resulted in decreasing antagonist activity. Changing Leu11 to D-Leu11 and D-Ala11 reduced antagonist activity. [D-Arg1,D-Pro2,D-Trp7,D-Trp9,Leu11]-SP is the most potent antagonist of this group of analogs, and required a 100-fold increase in the concentration of SP to give 50% of the maximal response caused by SP.     

Cyclooxygenase inhibitors derived from thalidomide

Several N-3,5-dimethylphenylphthalimide analogs possessing more potent cyclooxygenase-inhibiting activity than that of aspirin were prepared during structural development studies based on thalidomide. Substituent effects on the activity were investigated.     

Cyclophosphites from Oligomethylenephenols

New types of oligomethylenephenol cyclophosphites containing 1-3 phosphorus atoms are synthesized by reactions of available oligomethylenephenols with phosphorous acid amides. Contrary to their simple analogs, the resulting phosphites are stable on handling, which allowed design on their basis of complex coordination systems holding promise for metal complex catalysis.     

Synthesis of N‐Aryl Formyl Pyrrole from γ‐Lactam Derivatives: A Highlight

Pyrrole containing analogs are considered as a potential source of biologically active compounds and have significant set of advantageous properties and are found in many natural products. A number of methods have been reported till now to synthesize pyrrole and pyrrole containing analogs. This review article outlines highlight the recent progresses in pyrrole synthesis from γ‐lactam derivatives.     

Synthesis of pyridines from dicyanopyrimidines. A diels-alder approach to the c-ring of streptonigrin

The reaction of dicyanopyrimidines with yneamines gave pyridines which could potentially serve as precursors to analogs of streptonigrin.     

Use of semi-empirical models for calculation of B terms in MCD spectra. Aromatic hydrocarbons: prediction of substituent and heteroatom effects from PPP model

Sign patterns in magnetic circular dichroic (MCD) spectra of derivatives and hetero analogs of uncharged alternant hydrocarbons (“soft MCD chromophores”) are determined by the nature and location of the substituent or heteroatoms in a simply predictable way, while those for derivatives and hetero analogs of charged alternant hydrocarbons and of non-alternant hydrocarbons (“hard MCD chromophores”) are characteristic of the parent chromophore.     

Triterpenoids from Melia toosendan

Eleven new triterpenoids, named mesendanins K–U ( 1 – 11 , resp.), together with seven known analogs, were isolated from the leaves and twigs of Melia toosendan. Their structures were elucidated on the basis of extensive spectroscopic analysis.     

Simple synthesis of disodium phosphates of racemic 2,3-dihydroprenols from plant polyprenols

Russian Chemical Bulletin - A simple method of synthesis of (±)-2,3-dihydroprenol disodium phosphates, semisynthetic analogs of natural dolichyl phosphate, was developed. The method consists...