Nucleotide-binding oligomerization domain protein 1 (NOD1) belongs to a family that includes multiple members with NOD and leucine-rich repeats in vertebrates and plants. NOD1 has been suggested to have a role in innate immune responses, but the mechanism involved remains unknown. Here we report that NOD1 mediates the recognition of peptidoglycan derived primarily from Gram-negative bacteria. Biochemical and functional analyses using highly purified and synthetic compounds indicate that the core structure recognized by NOD1 is a dipeptide, γ-D-glutamyl-meso-diaminopimelic acid (iE-DAP). Murine macrophages deficient in NOD1 did not secrete cytokines in response to synthetic iE-DAP and did not prime the lipopolysaccharide response. Thus, NOD1 mediates selective recognition of bacteria through detection of iE-DAP-containing peptidoglycan. *Note: In the version of this article initially published online, one author's first name and last name were reversed. The correct author name should be Su Qiu. This mistake has been corrected for the HTML and print versions of the article.

An essential role for NOD1 in host recognition of bacterial peptidoglycan containing diaminopimelic acid.

Recent developments in the stereoselective synthesis of α-aminoacids

2,5-Diketopiperazines: synthesis, reactions, medicinal chemistry, and bioactive natural products.

https://www.cell.com/cell/pdf/S0092-8674(85)80031-3.pdf

Production of abnormal proteins in E. coli stimulates transcription of ion and other heat shock genes

Fosmidomycin, a specific inhibitor of 1-deoxy-d-xylulose 5-phosphate reductoisomerase in the nonmevalonate pathway for terpenoid biosynthesis

A compound of the formula :
 wherein R 1 is lower alkyl optionally substituted with a substituent selected from the group consisting of acyl,hydroxy, lower alkoxy, aryl, lower alkylthio and a group of the formula :
 in which R 5 is hydrogen or acyl and
 R 6 is hydrogen or lower alkyl; aryl; or amino optionally substituted with substituent(s) selected from the group consisting of lower alkyl and acyl; and R 2 is hydrogen or lower alkyl; or R 1 and R 2 are taken together with the attached nitrogen atom to form a heterocyclic group optionally substituted with substituent(s) selected from the group consisting of lower alkyl, hydroxy(lower)alkyl, lower alkoxy(lower)alkyl, acyl(lower)alkyl, oxo and acyl; R 3 is hydrogen or lower alkyl; and R 4 is lower alkyl; and its pharmaceutically acceptable salt, processes for the preparation thereof and pharmaceutical composition comprising the same.

New amino acid derivatives, processes for the preparation thereof and pharmaceutical composition comprising the same

The synthesis of analogs of 3-(N-acetyl-N-hydroxyamino) propylphosphonic acid (FR-900098, Ia) and an analysis of their structure-activity relationship are described. Among them, compounds Ib (FR-31564) and XIIb (FR-32863) have recently been found to be produced naturally by Streptomyces lavendulae. The antibacterial activity of Ib against Pseudomonas species is especially significant.

Studies on phosphonic acid antibiotics. IV. Synthesis and antibacterial activity of analogs of 3-(N-acetyl-N-hydroxyamino)-propylphosphonic acid (FR-900098).

Some (αR, βR) -1, β-dimethyltryptophans (5__∼) were prepared by the reaction of aziridine-2-carboxylates (4__∼), derived from D-threonine, and N-alkylindoles in the presence of BF3·OEt2.

SYNTHESIS OF OPTICALLY ACTIVE β-METHYLTRYPTOPHANS FROM AZIRIDINE-2-CARBOXYLATES

The invention deals with novel peptides useful for the therapeutic treatment of infectious diseases caused by pathogenic microorganisms. Included is the peptide FR900156 having the structure: ##STR1## as well as the peptides of the structure ##STR2## wherein R 1 is acyl; R b 1 is hydrogen, methyl, isopropyl, hydroxymethyl, protected hydroxymethyl or benzyl; R 2 is hydrogen, carboxy, protected carboxy, or a group of the formula: ##STR3## wherein R a 2 is mono- or di-carboxy lower alkyl or ar(carboxy) lower alkyl whose aryl moiety may be substituted by hydroxy, R b 2 is hydrogen or lower alkyl; R p and R q are each hydrogen, carboxy, protected carboxy, with proviso that when one of R 2 and R q is hydrogen, then the other is carboxy or protected carboxy; R r is hydrogen or amino protective group; m is an integer 1 to 3, and n is 1 .Iadd.provided that when R 1 is benzyloxycarbonyl R 5 1 is methyl, m is an integer 2 and n is an integer 1, then R 2 is not protected carboxy, and .Iaddend.provided that when R 1 is .[.hydrogen,.]. t-butoxycarbonyl or N-acetylmuramyl, R b 1 is methyl, m is an integer 2 and n is an integer 1, then R 2 is hydrogen, protected carboxy or a group of the formula: ##STR4## wherein R a 2 is mono- or di-carboxy lower alkyl having 1 and 3 to 6, carbon atoms, .[.α-carboxyethyl,.]. .Iadd.--CH 2 --CH 2 --COOH, .Iaddend.ar(carboxy) lower alkyl whose aryl moiety may be substituted by hydroxy and R b 2 is as defined above, or its pharmaceutically acceptable salt.

Peptide, process for preparation thereof and use thereof

The invention relates to a PAF-antagonist pharmaceutical composition comprising a compound of the formula: ##STR1## wherein R 1 is pyridyl(lower)alkyl or thiazolyl(lower)alkyl, R 2 is N-lower alkylindolyl(lower)alkyl which may have lower alkyl or halogen on the indole ring, and R 3 and R 4 are each hydrogen or lower alkyl; or pharmaceutically acceptable salt thereof.

Keiji Hemmi

Papers

New amino acid derivatives, processes for the preparation thereof and pharmaceutical composition comprising the same

Studies on phosphonic acid antibiotics. IV. Synthesis and antibacterial activity of analogs of 3-(N-acetyl-N-hydroxyamino)-propylphosphonic acid (FR-900098).

SYNTHESIS OF OPTICALLY ACTIVE β-METHYLTRYPTOPHANS FROM AZIRIDINE-2-CARBOXYLATES

Peptide, process for preparation thereof and use thereof

Piperazine compound as PAF-antagonist