Drug delivery systems: optimising the structure of peptide carriers for synthetic antimicrobial drugs

This paper discusses the concept of smugglins, i.e., molecules that are formed by attaching to, or incorporating into, normal cell nutrients varied moieties as a means of transporting otherwise impermeant substances into cells. Examples of antimicrobial smugglins that use this principle in Nature are described. The rationally designed antibiotic smugglins investigated to date are critically reviewed. Criteria for the design of optimal peptide carriers for antimicrobial smugglins are considered. A computer-linked, continuous-flow system for rapid measurement of the kinetic parameters for substrate transport via peptide permeases is described which, together with current molecular, genetic and biochemical techniques, now provides the means to obtain the information on which rational design should be based; examples are given for Escherichia coli and Candida albicans. After an uncertain commercial start, it now seems likely that increasing understanding of the uptake processes and other relevant features will make drug targeting using peptide carriers an achievable goal. Certainly their widespread occurrence in Nature should provide added incentive for the design of synthetic smugglins.