Synthetic analogues 302 Subject

Retinoids are a family of naturally occurring and synthetic analogues of vitamin A. The skin of subjects deficient in vitamin A becomes hyperplastic and keratotic (phrynoderma, or toad skin). While natural vitamin A is occasionally employed therapeutically, synthetic retinoids are more effective and represent a major advance in dermatological pharmacotherapy. Retinoids have myriad effects on cellular differentiation and proliferation it is likely that nuclear retinoic acid receptors mediate these effects by activating gene expression in a manner analogous to receptors for steroid hormones and thyroid hormones. Despite a common mechanism of action, however, retinoids vary widely in their physiological effects. 

This group of compounds is widely found in nature as metal complexes in the chlorophylls, the haem groups of many iron proteins and the corrinoids. They have in common a macrocyclic structure which provides four N donor atoms at the comers of a square plane. Metal coordination to the N atoms results in the displacement of two H+ ions. An extremely important feature of these molecules is their extensive -electron delocalization. The complexation of these and synthetic analogues has been the subject of a number of texts.143-145 Some of these aspects are also covered by Dolphin (Chapter 21,1), and biological related properties by Hughes (Chapter 62.1). 

A Acetylation, O-Phosphorylation, and O-Adenylylation. A/-Acetylation, O-phosphorjiation, and O-adenyljiation provide mechanisms by which therapeutically valuable aminocyclitol antibiotics, eg, kanamycia [8063-07-8] gentamicin [1403-66-3] sisomicin [32385-11-8], streptomycia [57-92-1], neomycin, or spectinomycin are rendered either partially or completely iaactive. Thus, eg, kanamycia B [4696-78-8] (50) can be iaactivated by modification at several sites, as shown. The elucidation of these mechanisms has allowed chemical modification of the sites at which the iaactivation occurs. Several such bioactive analogues, eg, dibekacia and amikacin have been prepared and are not subject to the iaactivation hence, they inhibit those organisms against which the parent antibiotics are iaeffective (96) (see Antibacterial agents, synthetic). 

The minimal cell, as the simplest system which has all the required properties of life (metabolism, self-reproduction and the ability to evolve), is presently studied as part of a new research discipline synthetic biology. This includes subjects such as synthesis in branches of biological systems, for example, of new RNA species, new peptides and new nucleic acid analogues, as well as the synthesis of peptide nucleic acids. One example is the work of M. R. Ghadiri and G. von Kiedrowski on self-replication of oligonucleotides and oligopeptides (Luisi, 2006b). 

Natural disturbance patterns can be very important when evaluating the likelihood of recovery from anthropogenic stressors. Ecosystems that have been subjected to repeated natural disturbances may be more vulnerable to anthropogenic stressors (e.g., overfishing). Alternatively, if an ecosystem has become adapted to a disturbance pattern, it may be affected when the disturbance is removed (fire-maintained grasslands). The lack of natural analogues makes it difficult to predict recovery from novel anthropogenic stressors such as exposure to synthetic chemicals. 

---