The present study describes the synthesis and biological studies of a small series of head-to-tail cyclic tetrapeptides of the general structure c(Lys‐β2,2‐Xaa‐Lys) containing one lipophilic β2,2-a ...
The prevalence of carbapenemase-producing Enterobacteriaceae (CPE) is increasing worldwide. Here we present associated patient data and molecular, epidemiological and phenotypic characteristics of all CPE isolates in Norway from 2007 to 2014 confirmed at the Norwegian National Advisory Unit on Detection of Antimicrobial Resistance. All confirmed CPE isolates were characterized pheno- and genotypically, including by whole genome sequencing (WGS). Patient data were reviewed retrospectively. In tot...
: The "golden era" of antibiotic discovery has long passed, but the need for new antibiotics has never been greater due to the emerging threat of antibiotic resistance. This urgency to develop new antibiotics has motivated researchers to find new methods to combat pathogenic microorganisms resulting in a surge of research focused around antimicrobial peptides (AMPs; also termed host defense peptides) and their potential as therapeutics. During the past few decades, more than 2000 AMPs have been ...
Abstract A library of small aminobenzamide derivatives was synthesised to explore a cationic amphipathic motif found in marine natural antimicrobials. The most potent compound E23 displayed minimal inhibitory concentrations (MICs) of 0.5–2 μg/ml against several Gram-positive bacterial strains, including methicillin resistant Staphylococcus epidermidis (MRSE) . E23 was also potent against 275 clinical isolates including Staphylococcus aureus , Enterococcus spp . , Escherichia coli , Pseudomonas a...
A practical and efficient methodology for the preparation of 2-aminoethyl α,α-disubstituted β-amino amides in three steps from methyl cyanoacetate has been developed. The key step in the synthesis was the chemoselective reduction of the nitrile group in presence of an amide and aryl halide functionalities. Reduction with RANEY® Nickel catalyst, either with molecular hydrogen (8–10 bar) or under transfer hydrogenation conditions, necessitated in situ protection of the resulting amines with Boc2O,...
Summary Background The declining efficacy of existing antibiotics potentially jeopardises outcomes in patients undergoing medical procedures. We investigated the potential consequences of increases in antibiotic resistance on the ten most common surgical procedures and immunosuppressing cancer chemotherapies that rely on antibiotic prophylaxis in the USA. Methods We searched the published scientific literature and identified meta-analyses and reviews of randomised controlled trials or quasi-rand...
Antibiotic resistance is spreading faster than the introduction of new compounds into clinical practice, causing a public health crisis. Most antibiotics were produced by screening soil microorganisms, but this limited resource of cultivable bacteria was overmined by the 1960s. Synthetic approaches to produce antibiotics have been unable to replace this platform. Uncultured bacteria make up approximately 99% of all species in external environments, and are an untapped source of new antibiotics. ...
#2Jordi Carratalà(ISCIII: Carlos III Health Institute)H-Index: 75
Bacterial infection is one of the most frequent complications in cancer patients and hematopoietic stem cell transplant recipients. In recent years, the emergence of antimicrobial resistance has become a significant problem worldwide, and cancer patients are among those affected. Treatment of infections due to multidrug-resistant (MDR) bacteria represents a clinical challenge, especially in the case of Gram-negative bacilli, since the therapeutic options are often very limited. As the antibiotic...
We have in the present study explored the anticancer activity against human Burkitt's lymphoma cells (Ramos) of a series of small linear and cyclic tetrapeptides containing a β2,2-amino acid with either two 2-naphthyl-methylene or two para-CF3-benzyl side chains, along with their interaction with the main plasma protein human serum albumin (HSA). The cyclic and more amphipathic tetrapeptides revealed a notably higher anticancer potency against Ramos cells [50% inhibitory concentration (IC50) 11–...
#1Hui-Min Xu(CAS: Chinese Academy of Sciences)H-Index: 2
#2Hua Yi(CAS: Chinese Academy of Sciences)H-Index: 1
Last. Ning-Hua Tan(CAS: Chinese Academy of Sciences)H-Index: 17
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Two novel cyclotetrapeptides, tataricins A and B, with a unique cyclopeptide backbone and a (Delta) (2,4)Pro side chain, were isolated from the traditional Chinese medicine Aster tataricus. Their structures and absolute configurations were determined using a combination of spectroscopic data, the advanced Marfey's method, and a total synthesis. Crown Copyright (C) 2012 Published by Elsevier Ltd. All rights reserved.
Synthesis and large-scale manufacturing technologies are now available for the commercial production of even the most complex peptide anti-infectives. Married with the potential of this class of molecule as the next generation of effective, resistance-free and safe antimicrobials, and a much better understanding of their biology, pharmacology and pharmacodynamics, the first regulatory approvals and introduction into clinical practice of these promising drug candidates will likely be soon. This i...
Last. Håvard Jenssen(RU: Roskilde University)H-Index: 40
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Antimicrobial peptides have attracted considerable interest as potential new class of antibiotics against multi-drug resistant bacteria. However, their therapeutic potential is limited, in part due to susceptibility towards enzymatic degradation and low bioavailability. Peptoids (oligomers of N-substituted glycines) demonstrate proteolytic stability and better bioavailability than corresponding peptides while in many cases retaining antibacterial activity. In this study, we synthesized a library...
Abstract Halogenation is widespread in Nature, as witnessed by the several thousands of naturally occurring halogenated compounds. This review seeks to provide an overview on the pathways and multiple roles of halogenation in Nature, as a source of inspiration to chemists. Remarkably, several halogenation pathways were recently found in humans, sparking an increasing interest into halogens as biomolecular recognition sites. A description of the molecular mechanisms underlining the role of haloge...
As a versatile therapeutic modality, peptides attract much attention because of their great binding affinity, low toxicity, and the capability of targeting traditionally "undruggable" protein surfaces. However, the deficiency of cell permeability and metabolic stability always limits the success of in vitro bioactive peptides as drug candidates. Peptide macrocyclization is one of the most established strategies to overcome these limitations. Over the past decades, more than 40 cyclic peptide dru...