1. Lactose esters: synthesis and biotechnological applications
Maciej Guzik, Jakub Staroń, Janusz M Dąbrowski, Ewelina Cichoń Crit Rev Biotechnol . 2018 Mar;38(2):245-258. doi: 10.1080/07388551.2017.1332571.
Biodegradable nonionic sugar esters-based surfactants have been gaining more and more attention in recent years due to their chemical plasticity that enables the various applications of these molecules. In this review, various synthesis methods and biotechnological implications of lactose esters (LEs) uses are considered. Several chemical and enzymatic approaches are described for the synthesis of LEs, together with their applications, i.e. function in detergents formulation and as additives that not only stabilize food products but also protect food from undesired microbial contamination. Further, this article discusses medical applications of LEs in cancer treatment, especially their uses as biosensors, halogenated anticancer drugs, and photosensitizing agents for photodynamic therapy of cancer and photodynamic inactivation of microorganisms.
2. Catalytic antibodies
A Tramontano, R A Lerner, K D Janda Science . 1986 Dec 19;234(4783):1566-70. doi: 10.1126/science.3787261.
Monoclonal antibodies elicited to haptens that are analogs of the transition state for hydrolysis of carboxylic esters behaved as enzymic catalysts with the appropriate substrates. These substrates are distinguished by the structural congruence of both hydrolysis products with haptenic fragments. The haptens were potent inhibitors of this esterolytic activity, in agreement with their classification as transition state analogs. Mechanisms are proposed to account for the different chemical behavior of these antibodies with two types of ester substrates. The generation of an artificial enzyme through transition state stabilization by antibodies was thus demonstrated. These studies indicate a potentially general approach to catalyst design.
3. Microbial esterases and ester prodrugs: An unlikely marriage for combating antibiotic resistance
Erik M Larsen, R Jeremy Johnson Drug Dev Res . 2019 Feb;80(1):33-47. doi: 10.1002/ddr.21468.
The rise of antibiotic resistance necessitates the search for new platforms for drug development. Prodrugs are common tools for overcoming drawbacks typically associated with drug formulation and delivery, with ester prodrugs providing a classic strategy for masking polar alcohol and carboxylic acid functionalities and improving cell permeability. Ester prodrugs are normally designed to have simple ester groups, as they are expected to be cleaved and reactivated by a wide spectrum of cellular esterases. However, a number of pathogenic and commensal microbial esterases have been found to possess significant substrate specificity and can play an unexpected role in drug metabolism. Ester protection can also introduce antimicrobial properties into previously nontoxic drugs through alterations in cell permeability or solubility. Finally, mutation to microbial esterases is a novel mechanism for the development of antibiotic resistance. In this review, we highlight the important pathogenic and xenobiotic functions of microbial esterases and discuss the development and application of ester prodrugs for targeting microbial infections and combating antibiotic resistance. Esterases are often overlooked as therapeutic targets. Yet, with the growing need to develop new antibiotics, a thorough understanding of the specificity and function of microbial esterases and their combined action with ester prodrug antibiotics will support the design of future therapeutics.
