The potential for new and resilient anti-cancer drugs based upon minor groove binders for DNA

Anti-infective and anticancer drugs share the serious problem that over time resistance develops to their effects leading to clinical obsolescence. Research at the University of Strathclyde has discovered a platform of anti-infective drugs based upon minor groove binders for DNA that have exceptional resilience to the development of resistance in their target organisms (bacteria, fungi, and parasites). This property is associated with the fact that the Strathclyde minor groove binders (S-MGBs) act at more than one discrete molecular target. One of the compounds has successfully completed a phase IIa clinical trial for the treatment of Clostridioides difficile infections. Several other compounds have shown activity against a number of cancer cell lines in vitro with indications of in vivo activity in a mouse model of lung cancer. This paper places these discoveries in the context of previous studies of minor groove binders as anticancer agents and considers whether the benefits of multitargeting successfully demonstrated in anti-infective applications can be translated to anticancer applications.

Engineered Modular Heterocyclic-Diamidines for Sequence-Specific Recognition of Mixed AT/GC Base Pairs at the DNA Minor Groove

This report describes a breakthrough in a project to design minor groove binders to recognize any sequence of DNA. A key goal is to invent synthetic chemistry for compound preparation...

Truncated S-MGBs: towards a parasite-specific and low aggregation chemotype

This paper describes the design and synthesis of Strathclyde minor groove binders (S-MGBs) that have been truncated by the removal of a pyrrole ring in order to mimic the structure of the natural product, disgocidine.

Evaluation of TaqMan Array card (TAC) for the detection of 28 respiratory pathogens

Background Respiratory infections are a serious threat to human health. So, rapid detection of all respiratory pathogens can facilitate prompt treatment and prevent the deterioration of respiratory disease. Previously published primers and probes of the TaqMan array card (TAC) for respiratory pathogens are not sensitive to Chinese clinical specimens. This study aimed to develop and improve the TAC assay to detect 28 respiratory viral and bacterial pathogens in a Chinese population. Methods To improve the sensitivity, we redesigned the primers and probes, and labeled the probes with minor groove binders. The amplification efficiency, sensitivity, and specificity of the primers and probes were determined using target-gene containing standard plasmids. The detection performance of the TAC was evaluated on 754 clinical specimens and the results were compared with those from conventional methods. Results The performance of the TAC assay was evaluated using 754 clinical throat swab samples and the results were compared with those from gold-standard methods. The sensitivity and specificity were 95.4 and 96.6%, respectively. The lowest detection limit of the TAC was 10 to 100 copies/μL. Conclusions TAC is an efficient, accurate, and high-throughput approach to detecting multiple respiratory pathogens simultaneously and is a promising tool for the identification of pathogen outbreaks.

Evaluation of TaqMan Array Card (TAC) for the Detection of 28 Respiratory Pathogens

Background: Respiratory infections are a serious threat to human health. So, rapid detection of all respiratory pathogens can facilitate prompt treatment and prevent the deterioration of respiratory disease. Previously published primers and probes of the TaqMan array card (TAC) for respiratory pathogens are not sensitive to Chinese clinical specimens. This study aimed to develop and improve the TAC assay to detect 28 respiratory viral and bacterial pathogens in a Chinese population. Methods: To improve the sensitivity, we redesigned the primers and probes, and labeled the probes with minor groove binders. The amplification efficiency, sensitivity, and specificity of the primers and probes were determined using target-gene containing standard plasmids. The detection performance of the TAC was evaluated on 754 clinical specimens and the results were compared with those from conventional methods.Results: The performance of the TAC assay was evaluated using 754 clinical throat swab samples and the results were compared with those from gold-standard methods. The sensitivity and specificity were 95.4% and 96.6%, respectively. The lowest detection limit of the TAC was 10 to 100 copies/μL. Conclusions: TAC is an efficient, accurate, and high-throughput approach to detecting multiple respiratory pathogens simultaneously and is a promising tool for the identification of pathogen outbreaks.