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161.
Whereas alpha-peptides are rapidly degraded in vivo and in vitro by a multitude of peptidases, substrates constructed entirely of or incorporating homologated alpha-amino acid (i.e., beta-amino acid) units exhibit a superior stability profile. Efforts made so far to proteolytically hydrolyze a beta-beta peptide bond have not proved fruitful; a study aimed at breaching this proteolytic stability is discussed here. A series of such bonds have been designed with side-chain groups similar in relative positions (constitution) and three-dimensional arrangements (configuration) as found about alpha-peptidic amide bonds. Increasing the prospect for degradation would permit the tuning of beta-peptide stability; here, however, no cleavage was observed (1, 2, 4-6, Table 1). Peptides comprised of alpha- and beta-amino acids (mixed alpha,beta-peptides, 8-11) are expected to benefit from both recognition by a natural receptor and a high level of proteolytic stability, ideal characteristics of pharmacologically active compounds. Beta3-peptides containing alpha-amino acid moieties at the N-terminus are degraded, albeit slowly, by several peptidases. Of particular interest is the ability of pronase to cleave an alpha-beta peptide bond, namely that of alphaAla-beta3 hAla. Significantly, successful hydrolysis is independent of the configuration of the beta-amino acid. Some of the alpha,beta-peptides discussed here are being investigated for their binding affinities to class I MHC proteins. The computer-programming steps required to prepare alpha,beta-peptides on an automated peptide synthesizer are presented. 相似文献
162.
McCabe SL Pelosi DM Tetreault M Miri A Nguitragool W Kovithvathanaphong P Mahajan R Zimmerman AL 《The Journal of general physiology》2004,123(5):521-531
Rod vision begins when 11-cis-retinal absorbs a photon and isomerizes to all-trans-retinal (ATR) within the photopigment, rhodopsin. Photoactivated rhodopsin triggers an enzyme cascade that lowers the concentration of cGMP, thereby closing cyclic nucleotide-gated (CNG) ion channels. After isomerization, ATR dissociates from rhodopsin, and after a bright light, this release is expected to produce a large surge of ATR near the CNG channels. Using excised patches from Xenopus oocytes, we recently showed that ATR shuts down cloned rod CNG channels, and that this inhibition occurs in the nanomolar range (aqueous concentration) at near-physiological concentrations of cGMP. Here we further characterize the ATR effect and present mechanistic information. ATR was found to decrease the apparent cGMP affinity, as well as the maximum current at saturating cGMP. When ATR was applied to outside-out patches, inhibition was much slower and less effective than when it was applied to inside-out patches, suggesting that ATR requires access to the intracellular surface of the channel or membrane. The apparent ATR affinity and maximal inhibition of heteromeric (CNGA1/CNGB1) channels was similar to that of homomeric (CNGA1) channels. Single-channel and multichannel data suggest that channel inhibition by ATR is reversible. Inhibition by ATR was not voltage dependent, and the form of its dose-response relation suggested multiple ATR molecules interacting per channel. Modeling of the data obtained with cAMP and cGMP suggests that ATR acts by interfering with the allosteric opening transition of the channel and that it prefers closed, unliganded channels. It remains to be determined whether ATR acts directly on the channel protein or instead alters channel-bilayer interactions. 相似文献
163.
Novel quinazolines, having interesting antibacterial activity have been prepared, characterized and tested against a panel of susceptible and resistant Gram positive and Gram negative organisms. 相似文献
164.
A systematic approach through computer assisted design to identify novel quinazolines having anxiolytic and GABAergic activity has been reported. 相似文献
165.
The aim of this work was to study the mutation profile in hMSH2 and hMLH1 genes in hereditary nonpolyposis colorectal cancer (HNPCC) patients in India. On the basis of the Bethesda criteria, 31 colorectal cancer patients were studied first for microsatellite instability, using the five markers recommended by the Bethesda guidelines. Twelve of 31 tumor samples were found to be MSI-H, 9 of 31 were MSI-L, and the rest were MSS. The 12 patients with MSI-H were analyzed for mutations in hMSH2 and hMLH1 genes using PCR-denaturing high-performance liquid chromatography (dHPLC), followed by sequencing of samples showing abnormal peaks. Of the five mutations detected, three were found to be deleterious mutations (hMSH2-R680X, hMLH1-E671X, and a splice junction mutation IVS16-2A --> G); one had a mutation of probable significance (hMLH1-C680G) and one was of unknown significance (hMSH2-R171K). This study has also shown that most of the early-onset colon (4/7) and early-onset rectal (15/21) cancers are MSS or MSI-L. This is the first study to describe the mutation in hMSH2 and hMLH1 in Indian patients, a low incidence region for colorectal cancer. A two-stage procedure using MSI testing followed by PCR-dHPLC was found to be an efficient method in studying the mutation profile in high-risk patients. 相似文献
166.
Harvinder Singh Saini Bhupinder Singh Chadha Shobha Bhaskar Surinder Singh Raman Kumar Minakshi Mahajan 《World journal of microbiology & biotechnology》1998,14(5):785-786
Of the nine actinomycete strains screened for their ability to grow on isomeric chlorobenzoates (Cba), Corynebacterium liquefaciens, a sewage isolate, was able to maximally metabolize 3.2mM 2- and 3-Cba in presence of 0.25mM glucose as co-substrate. The degradation of 2-Cba and 3-Cba was 70.3% and 79.37% (w/v), respectively, under optimized conditions. 相似文献
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Characterization of statistically produced xylanase for enrichment of fruit juice clarification process 总被引:1,自引:0,他引:1
Critical factors for xylanase production of Bacillus stearothermophilus under batch fermentation and for clarification of citrus fruit juice using this xylanase were optimized through central composite design of response surface methodology. Statistical approach resulted in an increase of 1.19-fold in xylanase yield over conventional method. Model equation for juice clarification included independent variables viz. temperature, incubation time and enzyme dose to study the dependent variables such as yield, acidic neutrality and filterability etc. Coefficient of determination, R(2) for enzyme production model and for different juice properties were in accordance with the linearity of the model. On the basis of the contour plots the optimum enzyme dose was 12.5 IU/g of xylanase. Enzymatic treatment has resulted in the improvement of twofold in the release of reducing sugars and 52.97% in juice yield, whereas 35.34% reduction in turbidity was observed. 相似文献