Therapeutic agents, peptide

Melatonin [73-31-4] C 2H N202 (31) has marked effects on circadian rhythm (11). Novel ligands for melatonin receptors such as (32) (12), C2yH2gN202, have affinities in the range of 10 Af, and have potential use as therapeutic agents in the treatment of the sleep disorders associated with jet lag. Such agents may also be usehil in the treatment of seasonal affective disorder (SAD), the depression associated with the winter months. Histamine (see Histamine and histamine antagonists), adenosine (see Nucleic acids), and neuropeptides such as corticotropin-like intermediate lobe peptide (CLIP) and vasoactive intestinal polypeptide (VIP) have also been reported to have sedative—hypnotic activities (7). 

Electrotransport technology offers a number of benefits for therapeutic appHcations, including systemic or local adininistration of a wide variety of therapeutic agents with the potential adininistration of peptides and proteins long-term noninvasive administration, improving convenience and compliance controlled release, providing a desired deflvery profile over an extended period with rapid onset of efficacious plasma dmg levels and in some cases reduced side effects and a transport rate relatively independent of skin type or site. Additional benefits include easy inception and discontinuation of treatment, patterned and feedback-controlled deflvery, and avoidance of first-pass hepatic metaboHsm. 

The development of peptides and proteins as therapeutic agents has been greatly accelerated by advances in the fields of biotechnology. 

Some of their derivatives have been used as antiviral drugs. Due to their flexible chemistry, they can be exploited to design drug delivery systems and in molecular nanotechnology. In such systems, they can act as a central lipophilic core and different parts like targeting segments, linkers, spacers, or therapeutic agents can be attached to the said central nucleus. Their central core can be functionalized by peptidic and nucleic acid sequences and also by numerous important biomolecules. 

High throughput methods have increased our capacity for appropriate candidate compounds selection and also for developing libraries of novel compounds from which such candidates can be selected. Chapter 7 discusses the use of solid-phase synthesis for the high throughput production of peptides and other small molecules. In addition, as discussed in Chapter 6 on peptidomimetics, the swift production of novel leads holds considerable promise for future discovery of novel therapeutic agents. 

Although the correlation between structural properties of aromatic hydrocarbons and their carcinogenic properties proved to be much more complicated than was hoped, this type of calculation opened the door to the application of quantum chemistry to biological systems. The calculations are applied not only to cancer-related problems, but also to the study of amino acids, peptides, nucleotides, and other than anti-cancer therapeutic agents. 

Conlon, J.M., Kolodziejek, J., and Nowotny, N. Antimicrobial peptides from ranid frogs taxonomic and phylogenetic markers and a potential source of new therapeutic agents, Biochim. Biophys. Acta, 1696, 1, 2004. 

Solid-phase synthesis of biomolecules, of which peptides are the prime example, is well established. The search for more effective therapeutic agents creates a need for different strategies to synthesize peptides with C-terminal end groups other than the usual carboxylic acid and carboxamide functionalities. Methods described herein are readily generalized to small nitrogen-containing organic molecules. 

Neilsen PE (1999) Peptide nucleic acids as therapeutic agents. Curr Opin Struct Biol 9 353-357 Nelson EM, Tewey KM, Liu LF (1984) Mechanism of antitumor drug action poisoning of mammalian DNA topoisomerase II on DNA by 4 -(9-acridinylamino)-methanesulfon-m-anisidide. Proc Natl Acad Sci U S A 81(5) 1361-1365... 

At first, combinatorial chemistry focused on peptide and nucleotide libraries synthesis, but because poor pharmacokinetical properties cause poor oral availability of this kind of molecule, there is increasing interest in the development of new methods to prepare small, drug-tike molecules which obey lipinski s mle of five [303]. Heterocyclic compounds can offer a high degree of structural diversity and have proven to be useful as therapeutic agents. For these, there are recent advances in the preparation of heterocycles on solid supports [304]. The examples reported in this section are organized by their ring size. 

Holz GG Chepumy OG (2003) Glucagon-like peptide-1 synthetic analogs New therapeutic agents for use in the treatment of diabetes melUtus. Curr Med Chem 10 2471-2483. 

The potential utility of peptides as therapeutic agents with clinical applications is limited as a consequence of intrinsic peptide properties such as metabolic instability or poor transmembrane mobility. Hence, the design and synthesis of meta-bolically stable peptide analogs that can either mimic or block the bioactivity of natural peptides or enzymes is an important area of medicinal chemistry research. Numerous structural modifications to peptides have been examined in pursuit of molecules with more desirable properties [1-3]. These modified structures, peptidomimetics, are nonpeptide molecules that imitate the desired properties of the natural substances. 

For many of the neuropeptides the receptors are known, and more recently non-peptidic, small-molecule antagonists have become available. Application of these antagonists will help to elucidate further the involvement of peptidic neurotransmitters within the nervous system, as well as their contribution to mental disturbances. It is also expected that some of the recently developed antagonists may become useful therapeutic agents. 

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