更新于：2024-11-01

Phospho-N-acetylmuramoyl pentapeptide transferase

更新于：2024-11-01

基本信息

别名-

简介-

关联

项与 Phospho-N-acetylmuramoyl pentapeptide transferase 相关的药物

PED-017

靶点

Phospho-N-acetylmuramoyl pentapeptide transferase

作用机制

磷酸-N-乙酰胞壁酰 - 五肽 - 转移酶抑制剂

在研机构

Pedanius Therapeutics Ltd.

原研机构

Pedanius Therapeutics Ltd.

在研适应症

铜绿假单胞菌感染

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

SQ-641

靶点

Phospho-N-acetylmuramoyl pentapeptide transferase

作用机制

磷酸-N-乙酰胞壁酰 - 五肽 - 转移酶抑制剂

在研机构

Sequella, Inc.

原研机构

Daiichi Sankyo Co., Ltd.

在研适应症

梭菌感染 [+2]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

SQ-922

靶点

Phospho-N-acetylmuramoyl pentapeptide transferase

作用机制

磷酸-N-乙酰胞壁酰 - 五肽 - 转移酶抑制剂

在研机构

Sequella, Inc. [+1]

原研机构

Daiichi Sankyo Co., Ltd.

在研适应症

梭菌感染 [+1]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 Phospho-N-acetylmuramoyl pentapeptide transferase 相关的临床结果

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100 项与 Phospho-N-acetylmuramoyl pentapeptide transferase 相关的转化医学

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0 项与 Phospho-N-acetylmuramoyl pentapeptide transferase 相关的专利（医药）

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项与 Phospho-N-acetylmuramoyl pentapeptide transferase 相关的文献（医药）

2020-09-15·ACS Omega3区 · 化学

Theoretical Study of Intermolecular Interactions between Critical Residues of Membrane Protein MraY_AAand Promising Antibiotic Muraymycin D2

3区 · 化学

ArticleOA

作者: Adhikari, Kamal ; Malek Zadeh, Saeid ; Rattinam, Rajesh ; Astani, Elahe K. ; Wang, Zhe-Chong ; Li, Tsung-Lin

Phospho-N-acetylmuramoyl-pentapeptide translocase (MraY_AA) from Aquifex aeolicus is the binding target for the nucleotide antibiotic muraymycin D2 (MD2). MraY_AA in the presence of the MD2 ligand has been crystallized and released, while the interactions between the ligand and active-site residues remain less quantitatively and qualitatively defined. We characterized theoretically the key residues involved in noncovalent interactions with MD2 in the MraY_AA active site. We applied the quantum theory of atoms in molecules and natural bond orbital analyses based on the density functional theory method on the solved crystal structure of MraY with the MD2 to quantitatively estimate the intermolecular interactions. The obtained results revealed the presence of multiple hydrogen bonds in the investigated active site with strength ranging from van der Waals to covalent limits. Lys70, Asp193, Gly194, Asp196, Gly264, Ala321, Gln305, and His325 are key active-site residues interacting with MD2. Conventional and unconventional hydrogen bonds in addition with charge-dipole and dipole-dipole interactions contribute significantly to stabilize the MD2 binding to the MraY_AA active site. It was also found that water molecules inside the active site have substantial effects on its structure stability through hydrogen-bonding interactions with MD2 and the interacting residues.

2020-02-20·Nucleosides, Nucleotides & Nucleic Acids

Synthesis and biological evaluation of a MraY selective analogue of tunicamycins

Article

作者: Katsuyama, Akira ; Matsumaru, Takanori ; Ichikawa, Satoshi ; Yokota, Shin-Ichi ; Yakushiji, Fumika ; Hikiji, Yuta ; Yamamoto, Kazuki ; Sato, Toyotaka

Tunicamycins, which are nucleoside natural products, inhibit both bacterial phospho-N-acetylmuraminic acid (MurNAc)-pentapeptide translocase (MraY) and human UDP-N-acetylglucosamine (GlcNAc): polyprenol phosphate translocase (GPT). The improved synthesis and detailed biological evaluation of an MraY-selective inhibitor, 2, where the GlcNAc moiety was modified to a MurNAc amide, has been described.

2019-12-01·The Journal of Antibiotics4区 · 医学

Liposidomycin, the first reported nucleoside antibiotic inhibitor of peptidoglycan biosynthesis translocase I: The discovery of liposidomycin and related compounds with a perspective on their application to new antibiotics

4区 · 医学

Review

作者: Kimura, Ken-Ichi

Liposidomycin is a uridyl liponucleoside antibiotic isolated from Streptomyces griseosporeus RK-1061. It was discovered by Isono in 1985, who had previously isolated and developed a related peptidyl nucleoside antibiotic, polyoxin, a specific inhibitor of chitin synthases, as a pesticide. He subsequently isolated liposidomycin, a specific inhibitor of bacterial peptidoglycan biosynthesis from actinomycetes, using a similar approach to the discovery of polyoxin. Liposidomycin has no cytotoxicity against BALB/3T3 cells but has antimicrobial activity against Mycobacterium spp. through inhibition of MraY (MurX) [phospho-N-acetylmuramoyl-pentapeptide transferase (translocase I, EC 2.7.8.13)]. Since the discovery of liposidomycin, several liposidomycin-type antibiotics, including caprazamycin, A-90289, and muraminomycin, have been reported, and their total synthesis and/or biosynthetic cluster genes have been studied. Most advanced, a semisynthetic compound derived from caprazamycin, CPZEN-45, is being developed as an antituberculosis agent. Translocase I is an interesting and tractable molecular target for new antituberculosis and antibiotic drug discovery against multidrug-resistant bacteria. This review is dedicated to Dr Isono on the occasion of his 88th birthday to recognize his role in the study of nucleoside antibiotics.