Peptide ligands in antibacterial drug discovery: use as inhibitors in target validation and target-based screening

Abstract

There is an urgent need to develop novel classes of antibiotics to counter the inexorable rise of resistant bacterial pathogens. Modern antibacterial drug discovery is focused on the identification and validation of novel protein targets that may have a suitable therapeutic index. In combination with assays for function, the advent of microbial genomics has been invaluable in identifying novel antibacterial drug targets. The major challenge in this field is the implementation of methods that validate protein targets leading to the discovery of new chemical entities. Ligand-directed drug discovery has the distinct advantage of having a concurrent analysis of both the importance of a target in the disease process and its amenability to functional modulation by small molecules. VITA is a process that enables a target-based paradigm by using peptide ligands for direct in vitro and in vivo validation of antibacterial targets and the implementation of high-throughput assays to identify novel inhibitory molecules. This process can establish sufficient levels of confidence indicating that the target is relevant to the disease process and inhibition of the target will lead to effective disease treatment.

Molluscicide screening and identification of novel targets against Pomacea canaliculata

“…The primary drug screening routes are phenotypic drug screening and target-based drug screening. [35][36][37] Phenotypic drug screening requires several compounds, and screening a new drug requires >100 000 compounds, making the process inefficient. 38 Compared with the phenotypic drug screening, the target-based drug development strategy possesses the advantages of high screening efficiency, clear objectives and targeted structural modification of the candidate compounds.…”

Antimicrobial, analgesic, DPPH scavenging activities and molecular docking study of some 1,3,5-triaryl-2-pyrazolines

“…VITA TM is a process that enables a target-based paradigm by using peptide ligands for direct in vitro and in vivo validation of antibacterial targets and the implementation of high-throughput assays to identify novel inhibitory molecules. This process can establish sufficient levels of confidence indicating that the target is relevant to the disease process and inhibition of the target will lead to effective disease treatment (Lapan et al, 2002).…”