Applications In Modern Medicine Research Articles

Chemoenzymatic and template-directed synthesis of bioactive macrocyclic peptides.

Non-ribosomally synthesized peptides have compelling biological activities ranging from antimicrobial to immunosuppressive and from cytostatic to antitumor. The broad spectrum of applications in modern medicine is reflected in the great structural diversity of these natural products. They contain unique building blocks, such as d-amino acids, fatty acids, sugar moieties, and heterocyclic elements, as well as halogenated, methylated, and formylated residues. In the past decades, significant progress has been made toward the understanding of the biosynthesis of these secondary metabolites by nonribosomal peptide synthetases (NRPSs) and their associated tailoring enzymes. Guided by this knowledge, researchers genetically redesigned the NRPS template to synthesize new peptide products. Moreover, chemoenzymatic strategies were developed to rationally engineer nonribosomal peptides products in order to increase or alter their bioactivities. Specifically, chemical synthesis combined with peptide cyclization mediated by nonribosomal thioesterase domains enabled the synthesis of glycosylated cyclopeptides, inhibitors of integrin receptors, peptide/polyketide hybrids, lipopeptide antibiotics, and streptogramin B antibiotics. In addition to the synthetic potential of these cyclization catalysts, which is the main focus of this review, different enzymes for tailoring of peptide scaffolds as well as the manipulation of carrier proteins with reporter-labeled coenzyme A analogs are discussed.

Nonribosomal Peptides: From Genes to Products

AbstractFor Abstract see ChemInform Abstract in Full Text.

Nonribosomal peptides: from genes to products.

The ability to synthesize nonribosomally small bioactive peptides that find application in modern medicine is widely spread among microorganisms. As broad as the spectrum of biological activities is the structural diversity of these peptides, which are mostly cyclic or branched cyclic compounds containing non-proteinogenic amino acids, small heterocyclic rings and other unusual modifications in the peptide backbone. They are synthesized by multimodular enzymes, the so-called nonribosomal peptide synthetases (NRPSs), from simple building blocks. Biochemical and genetic studies have unveiled the key principles of nonribosomal peptide syntheses, as well as the realization of many structural features of these peptides. This review focuses on recent results in NRPS research and highlights how this knowledge can be exploited for biotechnological purposes. In addition, possibilities and limitations for prediction of structural features of uncharacterized NRPSs and approaches for their engineering are discussed.

Cytotoxicity of EDTA used in biological samples: effect on some human breast-milk studies.

Ethylene diamine tetraacetic acid (EDTA) is a chelator for metal ions that has found widespread application in modern medicine and pharmacy. However, few studies have examined the cytotoxic side-effects of EDTA when added to biological samples upon various laboratory analyses. The present study was aimed at assessing the artefactual side-effects of EDTA on some biochemical assays performed on human milk samples. The secondary effects of addition of EDTA (at a final concentration of 20 mmol l(-1)) to inhibit complement system activation in human breast-milk samples were examined, using different laboratory techniques and methods, compared to milk samples with equivalent volumes of phosphate-buffered saline added. Assays considered included Biuret's test for total protein measurement, CH50 assays of whole complement activity, pH measurements and total cell counts. The toxic effects of EDTA included breast-milk cell loss, disruption of milk fat globule membrane and subsequent release of membrane-bound protein, free fatty acids and reduction in pH. It also caused false-positive results of haemolytic assays.

Plant folk medicines among Nicobarese tribals of Car Nicobar Island, India

The present paper deals with investigations of less known medicinal plant lore among the aboriginal Nicobarese tribe of Car Nicobar island, India. Information on 73 species and their therapeutic applications and manner of use are initially documented and described as remedies in folkloric tradition and popular domestic medicine. No chemical principles are identified; no putative herbal remedies are pharmaceutically and medically evaluated. The aim of this paper is to gather information concerning medicinal plants and to provide access to specialists in search of their applications in modern medicine. A brief account of geography, climate, ethnology, and methodology adopted is given. Vernacular name(s) of the plants in the Nicobarese language are incorporated for the first time in the literature.

Caffeine: a survey of some of the known and suspected deleterious effects of habitual use.

SummaryThe potential untoward consequences of habitual caffeine use are considered in terms of two broad classes of deleterious effects: (a) the symptom constellation known as‘caffeinism', and (b) a number of disease states in which caffeine may be an etiological factor. In addition, a brief overview is provided of recent attempts to assist heavy users to reduce caffeine intake to moderate and presumably safer levels.