- Evidence for α-lactone formation in the thioacetylation of some α-hydroxy acids with the aid of Mitsunobu-type reagent
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(S)-Mandelic acid, (S)-lactic acid, and (S)-2-hydroxy-3-phenylpropionic acid react with thioacetic acid in the presence of the salt of diisopropyl azodicarboxylate and triphenylphosphine to give the α-(acetylthio)-substituted products. (S)-Mandelic acid r
- Strijtveen, Bert,Kellog, Richard M.
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- Design and synthesis of chromogenic thiopeptolide substrates as MetAPs active site probes
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Twenty one chromogenic thiopeptolide substrates were designed and synthesized as the active site probes and analyzed with each S1 site of mutant residues and enzymes of wild-type MetAP1s. The preliminary enzymatic experiments indicate that cysteine 70 or 202, at either Escherichia coli or human MetAP1, played a crucial role in the methionine hydrolysis.
- Cui, Yong-Mei,Li, Jing-Ya,Chen, Ling-Ling,Li, Jia,Ye, Qi-Zhuang,Nan, Fa-Jun
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p. 2853 - 2861
(2007/10/03)
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- Synthesis of optically pure (S)-2-acetylthio-3-benzenepropanoic acid via enzymatic resolution
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A method of synthesizing optically pure (S)-2-acetylthio-3-benzenepropanoic acid has been developed and good to excellent enantiomeric excess achieved via enzymatic resolution.
- Zhu, Jingyang,You, Li,Zhao, Shannon X,White, Brenda,Chen, Jason G,Skonezny, Paul M
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p. 7585 - 7587
(2007/10/03)
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- Synthesis and SAR of thioester and thiol inhibitors of IMP-1 metallo-β-lactamase
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Potent thioester and thiol inhibitors of IMP-1 metallo-β-lactamase have been synthesized employing a solid-phase Mitsunobu reaction as the key step.
- Greenlee, Mark L.,Laub, Joanne B.,Balkovec, James M.,Hammond, Milton L.,Hammond, Gail G.,Pompliano, David L.,Epstein-Toney, Jeffrey H.
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p. 2549 - 2554
(2007/10/03)
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- Optimal recognition of neutral endopeptidase and angiotensin-converting enzyme active sites by mercaptoacyldipeptides as a means to design potent dual inhibitors
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An interesting approach for the treatment of congestive heart failure and chronic hypertension could be to avoid the formation of angiotensin II by inhibiting angiotensin converting enzyme (ACE) and to protect atrial natriuretic factor by blocking neutral endopeptidase 24.11 (NEP). This is supported by recent results obtained with potent dual inhibitors of the two zinc metallopeptidases, such as RB 105, HSCH2CH(CH3)PhCONHCH(CH3)COOH (Fournie-Zaluski et al. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 4072-4076), which reduces blood pressure in experimental models of hypertension, independently of the salt and renin angiotensin system status. In order to develop new dual inhibitors with improved affinities, long duration of action, and/or better bioavailabilities, various series of mercaptoacyldipeptides corresponding to the general formula HSCH(R1)CONHCH(R1')CON(R)CH(R2')COOH have been synthesized. The introduction of well-selected β-branched chains in positions R1 and R1', associated with a tyrosine or a cyclic amino acid in the C-terminal position, led to potent dual inhibitors of NEP and ACE such as 21 [N-[(2S)-2-mercapto- 3-methylbutanoyl]-Ile-Tyr] and 22 [N-[(2S)-2-mercapte-3-phenylpropanoyl]Ala- Pro] which have IC50 values in the nanomolar range for NEP and subnanomolar range for ACE. These compounds could have different modes of binding to the two peptidases. In NEP, the dual inhibitors seem to interact only with the S1' and S2' subsites, whereas additional interactions with the S1 binding subsite of ACE probably account for their subnanomolar inhibitory potencies for this enzyme. The localization of the Pro residue of 22 outside the NEP active site is supported by biochemical data using (Arg102,Glu)NEP and molecular modeling studies with thermolysin used as model of NEP. One hour after oral administration in mice of a single dose (2.7 x 10-5 mol/kg), 21 inhibited 80% and 36% of kidney NEP and lung ACE, respectively, while 22 inhibited 40% of kidney NEP and 56% of lung ACE.
- Coric, Pascale,Turcaud, Serge,Meudal, Hervé,Roques, Bernard Pierre,Fournie-Zaluski, Marie-Claude
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p. 1210 - 1219
(2007/10/03)
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- Synthesis of C2-symmetric HIV-protease inhibitors with sulfur-containing central units
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Sulfide-, sulfoxide-, and sulfone- containing C2-symmetric peptide analogs were obtained stereospecifically starting from phenylalanine. The compounds were evaluated as potential HIV-protease inhibitors and found to be inactive within the limit
- Spaltenstein,Leban,Furfine
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p. 1457 - 1460
(2007/10/02)
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