ABSTRACT
Since oxidative cellular damage contributes to the development of cancers, heart disease and ageing, the synthesis of antioxidative agents which are able to either prevent or mitigate oxidative stress to cells is an important area of investigation. Combinatorial chemistry has had a profound impact on the discovery and optimisation of potential lead compounds, especially in the medicinal field. This review details recent examples of combinatorial chemistry dealing with the synthesis of novel antioxidants with an emphasis on solid phase compound synthesis and parallel library synthesis.
Subject(s)
Antioxidants/chemistry , Antioxidants/chemical synthesis , Peptide Library , Caffeic Acids/chemistry , Combinatorial Chemistry Techniques , Indazoles/chemistry , Molecular Structure , Propylene Glycols/chemistry , Quinones/chemistryABSTRACT
Combinatorial chemistry has had a major impact on the discovery and optimisation of potential lead compounds. This review details some of the fundamental principles behind combinatorial chemistry and describes a variety of methods employed in the search for new therapeutically interesting compounds including the concept of dynamic combinatorial chemistry as a method of selecting active compounds from a mixture. It also outlines methods used to analyse resin bound products and describes how solution phase library generation may be aided by the use of resin bound reagents and scavengers.
Subject(s)
Combinatorial Chemistry Techniques/methods , Drug Design , Pharmaceutical Preparations/chemical synthesis , Molecular ConformationABSTRACT
Using a highly efficient solid-phase route a series of fluorescein conjugated peptoid oligomers were synthesised and observed to display remarkable cell penetrating properties, offering the possibility of highly efficient cellular targeting.
Subject(s)
Carrier Proteins/chemical synthesis , Peptoids/chemical synthesis , Animals , Carrier Proteins/chemistry , Carrier Proteins/pharmacokinetics , Cell Line , Cell Line, Tumor , Flow Cytometry/methods , Fluoresceins/chemistry , Humans , Mice , Models, Chemical , Molecular Structure , Peptoids/chemistry , Peptoids/pharmacokineticsABSTRACT
Two new probes for the detection of calpain I activity based on fluorescence resonance energy transfer technology have been synthesized and evaluated. The probes incorporated the cleavage site present in alpha-spectrin, a naturally occurring substrate of calpain I. The design of the internally quenched substrates is such that the calpain-sensitive bond of the peptides (between the Tyr-Gly residues) is located centrally between the donor and the quencher chromophores. The calpain assay protocol is capable of detecting enzymatic activity in the nanomolar region.