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21.
A step leading to the formation of the covalent complexes between porcine pancreatic elastase (PPE) and 7-[(alkylcarbamoyl)amino]-4-chloro-3-ethoxyisocoumarins (alkylHNCO-EICs) is the formation of the noncovalent Michaelis complex. No average structures are available for the Michaelis complexes of PPE with alkylHNCO-EICs. We present the results of an initial step in obtaining these structures and have determined kinetic constants as well. The kinetic results indicate that formation of the Michaelis complex is what differentiates the effectiveness of these inhibitors in inactivating PPE. The structural and kinetic results together suggest that the structure of the Michaelis complex is necessary for the design of potent alkylHNCO-EIC inhibitors of PPE. Two novel alkylHNCO-EICs are predicted to be the best inhibitors of this series. An alternate mechanism for serine protease inhibition is also proposed. Evidence for, and studies that may add support to, the hypothesized mechanism are discussed. 相似文献
22.
This study examines the optimal seasonal timing of the life cycle for univoltine and bivoltine insects, assuming that resource
availability has a peak in the middle of a year and is symmetric around it. Results show that if the growth rate increases
in proporrion to the bodyweight, bivoltine life cannot be optimal. If the growth rate is a power function of the bodyweight
with a power smaller than unity, a symmetric bivoltine solution can be the optimal provided that the resource availability
has a plateau in the middle of the season. If the resource availability has a sharp peak, the optimal pattern is an asymmetric
bivoltine solution in which the larval periods of two generations differ in length. The bivoltine life cycle is more likely
to be superior to the univoltine one if: growth is fast, suitable growing season is long, biomass loss during nonlarval stages
is small, and egg size is small. 相似文献
23.
The design of single-stranded nucleic acid knots 总被引:1,自引:0,他引:1
Nadrian C. Seeman 《Molecular Engineering》1992,2(3):297-307
A general strategy is described for the synthesis of single-stranded nucleic acid knots. Control of nucleic acid sequence is used to direct the formation of secondary structures that produce the target topology. The key feature of the strategy is the equation of a half-turn of double helical DNA or RNA with a node in a knot. By forming nodes from complementary DNA sequences, it appears possible to direct the assembly of any simple knot. Stabilization of individual nodes may be achieved by constructing them from long regions containing both B-DNA and Z-DNA. Control over the braiding of DNA that acts as a link between node-forming domains can be realized by condensing the nodes into well-defined DNA structures, such as extended domains of linear duplex, branched junctions, antijunctions or mesojunctions. Further topological control may be derived from the pairing of linker regions to complementary single-stranded molecules, thereby preventing them from braiding in an undesirable fashion. 相似文献
24.
25.
26.
Twelve- and sixteen-residue peptides have been designed to form tetrameric alpha-helical bundles. Both peptides are capable of folding into amphiphilic alpha-helices, with leucyl residues along one face and glutamyl and lysyl residues along the opposite face. Four such amphiphilic alpha-helices are capable of forming a noncovalently bonded tetramer. Neighboring helices run in antiparallel directions in the design, so that the complex has 222 symmetry. In the designed tetramer, the leucyl side chains interdigitate in the center in a hydrophobic interaction, and charged side chains are exposed to the solvent. The designed 12-mer (ALPHA-1) has been synthesized, and it forms helical aggregates in aqueous solution as judged by circular dichroic spectroscopy. It has also been crystallized and characterized by x-ray diffraction. The crystal symmetry is compatible with (but does not prove) the design. The design can be extended to a four-alpha-helical bundle formed from a single polypeptide by adding three peptide linkers. 相似文献
27.
28.
The inhibiting effect of 14 typical creosote compounds on the aerobic degradation of toluene was studied in batch experiments. Four NSO-compounds (pyrrole, 1-methylpyrrole, thiophene, and benzofuran) strongly inhibited the degradation of toluene. When the NSO-compounds were present together with toluene, little or no degradation of toluene was observed during 16 days of incubation, compared with a total removal of toluene within 4 days when the four compounds were absent. Indole (an N-compound) and three phenolic compounds (phenol, o-cresol, and 2,4-dimethylphenol) also inhibited the degradation of toluene, though the effect was much weaker that of the four NSO-compounds. O-xylene, p-xylene, naphthalene and 1-methylnaphthalene seemed to stimulate the degradation even though the influence was very weak. No effects of benzothiophene (an S-compound) and quinoline (an N-compound) were observed. Benzofuran (an O-compound) was identified as the compound that most inhibited the degradation of toluene. An effect could be detected even at low concentrations (40 g/l).Abbreviations bf
benzofuran
- bt
benzothiophene
- dmp
2,4-dimethylphenol
- GC
gas chromatograph
- ind
indole
- mnap
1-methylnaphthalene
- MAH
monoaromatic hydrocarbons
- mpyr
1-methylpyrrole
- nap
naphthalene
-
o-cre
o-cresol
-
o-xyl
o-xylene
- phe
phenol
- pyr
pyrrole
-
p-xyl
p-xylene
- tol
toluene
- thi
thiophene
- qui
quinoline 相似文献
29.
A note on optimality in lattice square designs 总被引:1,自引:0,他引:1
30.
Takeshi Kikuchi 《Journal of Protein Chemistry》1996,15(6):539-545
In a previous paper we demonstrated that the short-range compact regions in atrial natriuretic factor (-hANF) predicted by the average distance map (ADM) correspond to its active sites [Kikuchi,J. Protein Chem.11, 579–581 (1992)]. In the present paper we apply the same method to other bioactive peptides and peptidic enzyme inhibitors. We again observe that active sites in each peptide are contained in short-range compact regions predicted by the ADM for the peptide. This demonstrates that the ADM method predicts the possible location of active sites in biologically active peptides in general. The possibility of practical application of the present method to rational drug design is also discussed. 相似文献