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Certain neuropeptides are known to cause a hypotensive response, thought to be due to mast cell degranulation. The effects of five antagonists of luteinizing hormone-releasing hormone on blood pressure and heart rate were compared in the anesthetized rat. When given intravenously, all five compounds induced hypotensive and bradycardiac effects. The order of potency for these effects was Nal-Arg Antagonist approximately detirelix [( N-Ac-D-Nal(2)1, D-pCl-Phe2,D-Trp3,D-hArg(Et2)6,D-Ala10]LHRH) greater than [N-Ac-D-Nal(2)1, D-pCl-Phe2,D-Pal(3)3,D-hArg(Et2)6,L-hArg (Et2)8,D-Ala10]LHRH (RS-26306) approximately antide greater than [N-Ac-D-Nal(2)1, D-pCl-Phe2,D-Pal(3)3,6, L-hArg(Et2)8,D-Ala10]LHRH (RS-15378) and did not parallel the order of antiovulatory potencies of these compounds. The hypotensive activity of LHRH antagonists, therefore, appeared dissociable from their antiovulatory activity. RS-26306 and RS-15378 appeared to have the greatest therapeutic ratios. 相似文献
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C Crone J Frokjaer-Jensen JJ Friedman O Christensen 《The Journal of general physiology》1978,71(2):195-220
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Understanding the structural and dynamic determinants of binding free energy in the antigen-antibody bond is of great interest. Much work has focused on selective mutations in order to locate key interaction residues, but this generally results in reduced affinity. The present work instead examines a higher-affinity mutant to characterize the thermodynamic pathway of the affinity maturation process. We have compared the antigen binding energetics of scFv D1.3, an anti-hen egg lysozyme single chain antibody, with a higher-affinity mutant (Hawkins, R. E., Russell, S. J., Baier, M. and Winter, G. (1993). J. Mol. Biol. 234, 958-964). The mutant has five-fold higher affinity for lysozyme but nearly the same enthalpy and heat capacity change upon binding, as measured by isothermal titration calorimetry. Thus, much of the binding free energy difference can be attributed to entropic effects. Fluorescence quenching with acrylamide indicates that this more favorable entropy change may result from a more flexible mutant-lysozyme complex and thus be a configurational entropy effect. 相似文献
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Lipoteichoic acid is an important microbe-associated molecular pattern of Lactobacillus rhamnosus GG
Claes Ingmar JJ Segers Marijke E Verhoeven Tine LA Dusselier Michiel Sels Bert F De Keersmaecker Sigrid CJ Vanderleyden Jos Lebeer Sarah 《Microbial cell factories》2012,11(1):1-8