127977-22-4Relevant academic research and scientific papers
Macrocyclic Peptides that Selectively Inhibit the Mycobacterium tuberculosis Proteasome
Zhang, Hao,Hsu, Hao-Chi,Kahne, Shoshanna C.,Hara, Ryoma,Zhan, Wenhu,Jiang, Xiuju,Burns-Huang, Kristin,Ouellette, Tierra,Imaeda, Toshihiro,Okamoto, Rei,Kawasaki, Masanori,Michino, Mayako,Wong, Tzu-Tshin,Toita, Akinori,Yukawa, Takafumi,Moraca, Francesca,Vendome, Jeremie,Saha, Priya,Sato, Kenjiro,Aso, Kazuyoshi,Ginn, John,Meinke, Peter T.,Foley, Michael,Nathan, Carl F.,Darwin, K. Heran,Li, Huilin,Lin, Gang
supporting information, p. 6262 - 6272 (2021/05/29)
Treatment of tuberculosis (TB) currently takes at least 6 months. Latent Mycobacterium tuberculosis (Mtb) is phenotypically tolerant to most anti-TB drugs. A key hypothesis is that drugs that kill nonreplicating (NR) Mtb may shorten treatment when used in combination with conventional drugs. The Mtb proteasome (Mtb20S) could be such a target because its pharmacological inhibition kills NR Mtb and its genetic deletion renders Mtb unable to persist in mice. Here, we report a series of macrocyclic peptides that potently and selectively target the Mtb20S over human proteasomes, including macrocycle 6. The cocrystal structure of macrocycle 6 with Mtb20S revealed structural bases for the species selectivity. Inhibition of 20S within Mtb by 6 dose dependently led to the accumulation of Pup-tagged GFP that is degradable but resistant to depupylation and death of nonreplicating Mtb under nitrosative stress. These results suggest that compounds of this class have the potential to develop as anti-TB therapeutics.
MACROCYCLIC COMPOUNDS AS PROTEASOME INHIBITORS
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Paragraph 0346, (2019/05/02)
The compounds of the present invention are represented by the following compounds having Formula I and Formula (I'): where the substituents R1, R2, R2', R3, R4, R5, R', R", X, Y, and Z are as defined herein and where the substituents R1, R2, R3, R4, R5, R', R", X, Y, and Z are as defined herein. These compounds are used in the treatment of bacterial infections, parasite infections, fungal infections, cancer, immunologic disorders, autoimmune disorders, neurodegenerative diseases and disorders, inflammatory disorders, or muscular dystrophy or for providing immunosuppression for transplanted organs or tissues.
Preparation of Enantiomerically Pure Protected 4-Oxo-α-amino Acids and 3-Aryl-α-amino Acids from Serine
Jackson, Richard F. W.,Wishart, Neil,Wood, Anthony,James, Keith,Wythes, Martin J.
, p. 3397 - 3404 (2007/10/02)
The organozinc reagent 13, prepared from the protected β-iodo alanine derivative 3c using ultrasonic activation, is efficiently acylated using acid chlorides in the presence of bis(triphenylphosphine)palladium dichloride to give enantiomerically pure protected 4-oxo-α-amino acids 17 in 39-90percent yield (13 examples).Zinc reagent 13 can also be coupled with aryl iodides in the presence of bis(tri-o-tolylphosphine)palladium dichloride to give enantiomerically pure protected phenylalanine analogues 26, 29, and 30 in 10-67percent yield (11 examples).The reaction tolerates the presence of a variety of functional groups in the acid chloride and the aryl iodide and provides derivatives which can be easily deprotected, at either the carboxyl or amino terminus, to give intermediates suitable for peptide synthesis.
SYNTHESIS OF ENANTIOMERICALLY PURE PROTECTED β-ARYL ALANINES
Jackson, Richard F. W.,Wythes, Martin J.,Wood, Anthony
, p. 5941 - 5944 (2007/10/02)
The organozinc reagent (1), prepared from the β-iodoalanine derivative (2), reacts with aryl iodides at 50 deg C in the presence of catalytic bis(tri-o-tolylphosphine)palladium dichloride to give in moderate to good yields enantiomerically pure protected
