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931.
932.
Incorporation of unnatural amino acids and peptidomimetic residues into therapeutic peptides is highly efficacious and commonly employed, but generally requires laborious trial-and-error approaches. Previously, we demonstrated that C20 peptide has the potential to be a potential antiviral agent. Herein we report our attempt to improve the biological properties of this peptide by introducing peptidomimetics. Through combined alanine, proline, and sarcosine scans coupled with a competitive fluorescence polarization assay developed for identifying antiviral peptides, we enabled to pinpoint peptoid-tolerant peptide residues within C20 peptide. The synergistic benefits of combining these (and other) commonly employed methods could lead to a easily applicable strategy for designing and refining therapeutically-attractive peptidomimetics. 相似文献
933.
Modern evolutionary mechanics theories and resolving the programmed/non-programmed aging controversy
Theodore C. Goldsmith 《Biochemistry. Biokhimii?a》2014,79(10):1049-1055
Modern programmed (adaptive) theories of biological aging contend that organisms including mammals have generally evolved mechanisms that purposely limit their lifespans in order to obtain an evolutionary benefit. Modern non-programmed theories contend that mammal aging generally results from natural deteriorative processes, and that lifespan differences between species are explained by differences in the degree to which they resist those processes. Originally proposed in the 19th century, programmed aging in mammals has historically been widely summarily rejected as obviously incompatible with the mechanics of the evolution process. However, relatively recent and continuing developments described here have dramatically changed this situation, and programmed mammal aging now has a better evolutionary basis than non-programmed aging. Resolution of this issue is critically important to medical research because the two theories predict that very different biological mechanisms are ultimately responsible for age-related diseases and conditions. 相似文献
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938.
Rosamund E. Allen Theodore W. C. Lo Paul J. Thornalley 《Journal of Protein Chemistry》1993,12(2):111-119
Glyoxalase I (EC 4.4.1.5) was purified from human red blood cells by a simplified method using S-hexylglutathione affinity chromatography with a modified concentration gradient of S-hexylglutathione for elution. The pure protein had a specific activity of 1830 U/mg of protein, where the overall yield was 9%. The pure protein had a molecular mass of 46,000 D, comprised of two subunits of 23,000 D each, and an isoelectric point value of 5.1. TheK
M
value for methylglyoxal-glutathione hemithioacetal was 192±8 µM and thek
cat value was 10.9±0.2 × 104 min–1 (N = 15). The glyoxalase I inhibitor S-p-bromobenzylglutathione had aK
i
value of 0.16±0.04 µM and S-p-nitrobenzoxycarbonylglutathione, previously thought to inhibit only glyoxalase II, also inhibited glyoxalase I with aK
i
value of 3.12±0.88 µM. Reduced glutathione was a weak competitive inhibitor of glyoxalase I with aK
i
value of 18±8 mM. The polyclonal antibodies were raised to the purified enzyme and were found to react specifically with glyoxalase I antigen by immunoblotting. This procedure gave a protein of high purity with simple low pressure chromatographic techniques with a moderate but adequate yield for small-scale preparations. 相似文献
939.
Theodore L. Garber Austin L. Hughes Norman L. Letvin Joe W. Templeton David I. Watkins 《Immunogenetics》1993,38(1):11-20
To explore genetic mechanisms responsible for major histocompatibility complex (MHC) class I evolution in the artiodactyls, we cloned and sequenced MHC class I cDNAs from a Bos taurus bull heterozygous for cattle MHC (BoLA) class I serological specificities w2 and w30. Four unique cDNAs were found, indicating the presence of at least two MHC class I loci. Analysis of these four cDNAs and all previously published BoLA cDNA sequences suggested that there may be three cattle MHC class I loci. Additionally, comparison of all of the BoLA class I cDNAs to MHC class I cDNAs of other artiodactyls showed that some of the BoLA class I cDNAs were more similar to certain sheep cDNAs than they were to other cattle cDNAs. These data indicate that each BoLA class I locus has evolved independently after an ancestral gene duplication event and that inter-locus segmental exchange o or concerted evolution has not occurred rapidly enough to cause extensive divergence between the orthologous MHC class I loci of sheep and cattle.The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned the accession numbers L02832–L02835.
Correspondence to: T. L. Garber at the present address. 相似文献
940.
Theodore J. Angelopoulos Bart G. Denys Cathy Weikart Sergio G. Dasilva Timothy J. Michael Robert J. Robertson 《European journal of applied physiology and occupational physiology》1995,70(3):195-199
To determine the effect of endogenous opioids on catecholamine response during intense exercise [80% maximal oxygen uptake (
O2max)], nine fit men [mean (SE) (
O2max, 63.9 (1.7) ml · kg–1 · min–1; age 27.6 (1.6) years] were studied during two treadmill exercise trials. A double-blind experimental design was used with subjects undertaking the two exercise trials in counterbalanced order. Exercise trials were 20 min in duration and were conducted 7 days apart. One exercise trial was undertaken following administration of naloxone (N; 1.2 mmol · l–1; 3 ml) and the other after receiving a placebo (P; 0.9% saline; 3 ml). Prior to each experimental trial a flexible catheter was placed into an antecubital vein and baseline blood samples were collected. Immediately afterwards, each subject received bolus injection of either N or P. Blood samples were also collected after 20 min of continuous exercise while running. Epinephrine and norepinephrine were higher (P < 0.05) in the N than P exercise trial with mean (SE) values of 1679 (196) versus 1196 (155) pmol · l–1 and 24 (2.2) versus 20 (1.7) nmol · · l–1 respectively. Glucose and lactate were higher (P < 0.05) in the N than P exercise trial with values of 7 (0.37) versus 5.9 (0.31) mmol · l–1 and 6.9 (1.1) versus 5.3 (0.9) mmol · l–1 respectively. These data suggest an opioid inhibition in the release of catecholamines during intense exercise. 相似文献