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Biomedical subjects

J Chmielewski

Publications and source records attributed to J Chmielewski.

At least 37 records · Page 2Linked to original sources
PubMed1998

Inhibiting the assembly of protein-protein interfaces.

Protein-protein association is found throughout mechanisms of cellular growth and differentiation, and viral replication. Inhibiting the assembly of protein complexes, therefore, presents itself as a novel means of inhibition for a wide variety of cellular and viral events. Peptides and small molecules that modify the overall quaternary structure of a selection of receptor-ligand interactions and oligomeric viral enzymes have been developed recently.

HIV↗
PubMed1996

Subtilisin-catalyzed religation of proteolyzed hen egg-white lysozyme: investigation of the role of disulfides.

BACKGROUND: The use of proteases to form, instead of break, peptide bonds has expanded the repertoire of techniques available for protein semisynthesis. Several groups have previously reported the use of proteases in aqueous-organic solvents to form single amide bonds within proteins, but low yields and lengthy reaction times make this an impractical approach to protein synthesis. We recently found that proteolyzed triose phosphate isomerase can be re-ligated rapidly and efficiently by subtilisin, in mixed aqueous-organic solvent systems. RESULTS: We now report the use of subtilisin to resynthesize hen egg-white lysozyme from a mixture of its proteolyzed fragments in high yield and with rapid reaction times. This enzymatic religation can also be achieved after reduction of the four disulfide bonds present in lysozyme, with the same efficiency as that observed for the disulfide-containing proteolysis mixture. CONCLUSIONS: For egg-white lysozyme, the subtilisin religation reaction can be used to re-synthesize a proteolyzed protein even after reduction of disulfide bonds. The utility of this reaction in more generalized protein semisynthesis reactions is currently being explored.

Animals↗
PubMed1995

Synthesis of the basic-helix-loop-helix region of the immunoglobulin enhancer binding protein E47 and evaluation of its structural and DNA binding properties.

The basic-helix-loop-helix (bHLH) region of the immunoglobulin enhancer binding protein E47 (IEB E47) was prepared in high yield by a solid-phase peptide synthesis methodology. Size-exclusion chromatography, sedimentation equilibrium and cross-linking data showed that the synthetic bHLH protein, 1, was dimeric, and higher-order aggregates of trimer and tetramer were also observed. The circular dichroism spectrum of 1 showed a high helical content, which increased upon addition of DNA containing the kappa E2 sequence. Gel mobility shift experiments showed that protein 1 bound sequence specifically to the kappa E2 sequence with a binding constant of 10(-10) M2, and had an affinity for other E box sequences as well. Comparisons between the co-crystal structure of IEB E47 with DNA and structural studies in solution showed lower helical contents in solution as would have been predicted from the crystal structure.

Amino Acid Sequence↗
PubMed1994

The rational design of highly stable, amphiphilic helical peptides.

A computer algorithm was devised for the evaluation of helical stability of potentially amphiphilic peptide sequences of specified length containing a set number of leucines in the hydrophobic region. All possible combinations of Glu, Lys and Gln in the hydrophilic region are rated using a set of empirical rules for salt bridge formation in alpha-helices, and the sequences which rate the highest are displayed. The rules for salt bridge formation were largely derived from published studies on the effects of salt bridges on helical stability. The algorithm was tested by redesigning a known amphiphilic alpha-helical peptide, alpha 1B or 1, which has been shown to aggregate into four-helix bundles. Comparison of the circular dichroism spectra of two peptides, 2 and 3, to 1 demonstrated that the redesigned peptide with the highest priority score from the algorithm, 2, was more helical when aggregated and slightly more helical as a monomer, whereas the peptide with the low priority score, 3, was somewhat less helical when aggregated and much less helical when monomeric. These results support the design of the algorithm, although conclusions based on aggregation data are complicated by the importance of interhelix contacts in the bundle. Further studies are underway to examine the reliability of the algorithm's predictions regarding the design of other helical peptides.

Algorithms↗
PubMed1989

[Selenazoles. XII. (1) Reaction of 4-(p-tolyl)-selenosemi-carbazides of acetic, benzoic, isonicotinic, nicotinic and picolinic acid with omega-acetophenone].

The cyclization of 4-(p-tolyl)-selenosemicarbazides of acetic, benzoic, isonicotinic, nicotinic and picolinic acids (Ia-e) with omega-bromoacetophenone was investigated in the medium of methanol (Method A) or in methanol in the presence of anhydrous sodium acetate (Method B). Acid hydrolysis of compounds IIf-i and IVa-c, e was studied. Results of UV and IR spectrometric measurements and of the in vitro microbiological studies are presented. In contradistinction to corresponding thiosemicarbazides, the change in N4 nitrogen atom basicity of the parent selenosemicarbazide I (pKa of p-toluidine = 5.1), in comparison to that of 4-phenyl-selenosemicarbazide (pKa of aniline = 4.63), proved to influence the equilibrium of the reaction with omega-bromoacetophenone only in the methanol medium without addition of anhydrous sodium acetate (Method A).

Acetates↗
PubMed1979

[Respiratory tract in subjects occupationally exposed to asbestos dust].

Health status of 145 "isolators", in this 50 women, engaged in ship building and repair, inhalating asbestos dust for 2 to 24 years of occupation (10.7 and 1.7 years on average) was examined. High percentage (63.6) of chronic bronchitis was found, especially in those working more than 10 years, and more frequently in women. 13.3% of asbestos cases were diagnosed, in this in the group working longer than 15 years in 47.4%. In 20.6% of those examined, respiratory disfunction was noted, mainly obturative, with no changes in blood gases. Chronic bronchitis was found to have developed earlier and more frequently in women than in men, under the same exposure. This should be a contraindication to employ women on those work--stands where the air is considerably dusted by highly aggressive dusts.

Adult↗