Nocardicin A and B, monocyclic .beta.-lactam antibiotics from a Nocardia species

Hashimoto, Masashi; Komori, Tadaaki; Kitamura, Takashi

doi:10.1021/ja00426a063

Cited by 93 publications

(23 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A monobactam antibiotic, nocardicin, was isolated from Nocardia sp. (7), and a terpenoid brasilicardin with immunosuppressive activity was isolated from a clinical isolate (4).…”

mentioning

confidence: 99%

The complete genomic sequence of Nocardia farcinica IFM 10152

Ishikawa

Yamashita

Mikami

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

272

202

View full text Add to dashboard Cite

We determined the genomic sequence of Nocardia farcinica IFM 10152, a clinical isolate, and revealed the molecular basis of its versatility. The genome consists of a single circular chromosome of 6,021,225 bp with an average G؉C content of 70.8% and two plasmids of 184,027 (pNF1) and 87,093 (pNF2) bp with average G؉C contents of 67.2% and 68.4%, respectively. The chromosome encoded 5,674 putative protein-coding sequences, including many candidate genes for virulence and multidrug resistance as well as secondary metabolism. Analyses of paralogous protein families suggest that gene duplications have resulted in a bacterium that can survive not only in soil environments but also in animal tissues, resulting in disease.N ocardia are filamentous-growing Gram-positive soil saprophytes that belong to the family Actinomycetales, which also includes clinically and industrially important genera such as Mycobacterium, Streptomyces, Corynebacterium, and Rhodococcus. Many species of Nocardia cause the disease nocardiosis in humans and animals on lung, central nervous system, brain, and cutaneous tissues (1), and a species Nocardia asteroides is suspected to be an etiological agent of Parkinson's disease (2). Nocardiosis is on the rise, with an estimated 109-136 new cases occurring annually in Japan (3) and 500-1,000 in the U.S. (www.cdc.gov͞ncidod͞dbmd͞diseaseinfo͞nocardiosis t.htm). However, there are only a few studies on the mechanisms of nocardial virulence. Nocardia species are resistant to many front-line antibiotics. Because treatment for nocardiosis relies heavily on chemotherapy, their intrinsic multiple drug resistance is a serious problem.Another feature of the nocardia is that many strains, even clinical isolates, also have the capability to produce bioactive molecules such as antibiotics (4, 5) and enzymes that are industrially important (6). A monobactam antibiotic, nocardicin, was isolated from Nocardia sp. (7), and a terpenoid brasilicardin with immunosuppressive activity was isolated from a clinical isolate (4).Nocardia farcinica IFM 10152 was isolated from the bronchus of a 68-year-old male Japanese patient. Despite the complicated taxonomy of the nocardia, the species N. farcinica was found to be nearly homogeneous (8). Subsequently, to elucidate the molecular basis of the versatility of the nocardia, we analyzed the genomic sequence of N. farcinica IFM 10152. MethodsGenome Sequencing and Assembly. The nucleotide sequence of the N. farcinica IFM 10152 genome was determined by a wholegenome shotgun strategy. We constructed small-insert (2 kb) and large-insert (10 kb) genomic libraries and generated 127,077 sequences (giving 9-fold coverage) from both ends of the genomic clones. Sequence assembly was carried out by using the PHRED͞PHRAP͞CONSED package (9). Remaining gaps were closed by transcriptional sequencing (Nippon Gene, Toyama, Japan) or by primer walking. There were no ambiguous nucleotides in the genomic sequence that we could determine. Consistency of the final assembly was confirmed in terms of res...

show abstract

“…A monobactam antibiotic, nocardicin, was isolated from Nocardia sp. (7), and a terpenoid brasilicardin with immunosuppressive activity was isolated from a clinical isolate (4).…”

mentioning

confidence: 99%

The complete genomic sequence of Nocardia farcinica IFM 10152

Ishikawa

Yamashita

Mikami

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

272

202

View full text Add to dashboard Cite

show abstract

“…Maintaining the same tethering relationship, several hundred β-lactam analogs of nocardicin were also reported by Hofheinz and co-workers in 1981, Scheme 13 [55]. Nocardicin A, isolated in 1975, was the first reported monocyclic β-lactam with potentially useful antibacterial activity 58 [56]. The preparation employed the use of chiral β-amino acids 57, thereby ensuring the correct configuration at the 4-position of the lactam.…”

Section: Constrained Ugi Adducts From Bi-functional Precursorsmentioning

confidence: 90%

“Multi-component Reactions : Emerging Chemistry in Drug Discovery” ‘From Xylocain to Crixivan’

Hulme

Gore

2003

CMC

1,004

276

View full text Add to dashboard Cite

With the recent emergence of combinatorial chemistry and high-speed parallel synthesis for drug discovery applications, the multi-component reaction (MCR) has seen a resurgence of interest. Easily automated one-pot reactions, such as the Ugi and Passerini reactions, are powerful tools for producing diverse arrays of compounds, often in one step and high yield. Despite this synthetic potential, the Ugi reaction is limited by producing products that are flexible and peptide-like, often being classified as 'non drug-like'. This review details developments of new, highly atom-economic MCR derived chemical methods, which enable the fast and efficient production of chemical libraries comprised of a variety of biologically relevant templates. Representative examples will also be given demonstrating the successful impact of MCR combinatorial methods at different stages of the lead discovery, lead optimization and pre-clinical process development arenas. This will include applications spanning biological tools, natural products and natural product-like diversity, traditional small molecule and 'biotech' therapeutics respectively. In particular, this review will focus on applications of isocyanide based MCR (IMCR) reactions.

show abstract

“…Cispentacin exhibits a strong antifungal in vitro activity against various Candida strains, e.g., Candida albicans, Candida krusei and Candida utilis. It revealed its weakness in vitro activity against Trichophyton mentagrophytes, while not in vitro activity was observed against Cryptococcus and Aspergillus species [38][39][40]. Sitagliptin phosphate (Januvia TM ) was the first permitted drug to switch the blood glucose concentration [41].…”

Section: β-Lactammentioning

confidence: 99%

?-Amino Acids: Role in Human Biology and Medicinal Chemistry - A Review

Riaz¹,

Fazal-ur-Rehman²,

Ahmad³

2017

Med chem

View full text Add to dashboard Cite

Abstractβ-amino acids are an important class of macromolecules. They play role in life for survival. β-amino acids gained significant interest due to their interesting pharmaceutical uses as hypoglycemic, antiketogenic characteristics, sterile and antifungal activities, anthelminthic as well as potent insecticidal characteristics. These are vital building blocks for the preparation of pharmaceutical and agrochemical target molecules. These are utilized in development of drugs, bimolecular structure and molecular recognition. They are also important in treatment of different diseases which are viral to human health. They play important role in regulation of nutritional metabolism and immunity. It has also led to their wider adoption as intermediates in new drugs and has been a focus of considerable attention in medicinal chemistry. β-amino acids have found extensive applications as components of biologically active peptides and small molecule pharmaceuticals. Synthetic derivatives of biologically relevant peptides incorporating β-amino acids often display interesting pharmacological activity, with increased potency and enzymatic stability. β-peptides participate in arrangement of incredible stable auxiliary structures. This review summarizes recent developments about the different roles of β-amino acids in human biology and some implications in medicinal chemistry.

show abstract

Nocardicin A and B, monocyclic .beta.-lactam antibiotics from a Nocardia species

Cited by 93 publications

References 3 publications

The complete genomic sequence of Nocardia farcinica IFM 10152

The complete genomic sequence of Nocardia farcinica IFM 10152

“Multi-component Reactions : Emerging Chemistry in Drug Discovery” ‘From Xylocain to Crixivan’

?-Amino Acids: Role in Human Biology and Medicinal Chemistry - A Review

Contact Info

Product

Resources

About

Nocardicin A and B, monocyclic .beta.-lactam antibiotics from a Nocardia species

Cited by 93 publications

References 3 publications

The complete genomic sequence of Nocardia farcinica IFM 10152

The complete genomic sequence of Nocardia farcinica IFM 10152

&#x201C;Multi-component Reactions : Emerging Chemistry in Drug Discovery&#x201D; &#x2018;From Xylocain to Crixivan&#x2019;

?-Amino Acids: Role in Human Biology and Medicinal Chemistry - A Review

Contact Info

Product

Resources

About

“Multi-component Reactions : Emerging Chemistry in Drug Discovery” ‘From Xylocain to Crixivan’