126 Successful treatment of cepacia syndrome with a combination of intravenous antibiotics, oral cyclosporine and corticosteroids in a pediatric cystic fibrosis patient

Zaragoza, S.; Manonelles, G.; Biondi, Eric; Lubovich, S.; Rodriguez, Victorio; Ratto, P.; Fallo, Aurelia; Sordelli, N.; Vázquez, María; Galanternik, L.; Teper, A.

doi:10.1016/s1569-1993(17)30490-3

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“…Cyclic peptides have always been associated with enhanced oral administration because of their high permeability across the epithelial membrane and high stability against enzymatic degradation . For instance, two of the current commercially available oral peptide drugs are desmopressin (1) and cyclosporine (2) (Figure ), both are cyclic peptides and cyclosporine is also an NMAA‐rich peptide . Cyclosporine A, a hepta‐ N ‐methylated undecapeptide, is considered a chameleon molecule, meaning that, depending on the surrounding environment (either hydrophilic or lipophilic), it has the ability to modify its shape and polarity through intra‐molecular hydrogen bond interactions …”

Section: Introductionmentioning

confidence: 99%

N‐methylation in amino acids and peptides: Scope and limitations

et al. 2018

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Active pharmaceutical ingredients (APIs) can be divided into two types, namely chemical and biological entities. Traditionally, the former has been associated with the so-called small molecules. The revival of peptides in pharmaceutical industry results from their importance in many biological roles. However, low metabolic stability and the lack of oral availability of most peptides is the main drawback for peptide to fulfill that paradigmatic situation. In this regard, efforts are being channeled into addressing this issue by introducing restrictions into the flexible peptide backbone, mainly through N-methyl amino acids (NMAAs) or development of small cyclic peptides. In many cases, both the above restrictions are combined with the aim to enhance oral availability. The synthesis of NMAAs is complex and their introduction into the peptide chain brings additional synthetic challenges and also sometimes leads to side-reactions. Here we discuss the most efficient methods for the synthesis of NMAAs (either in solution or in solid phase) and also their introduction into peptide sequences. Special attention is also given to the detection of side reactions and the most efficient way to prevent them.

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Section: Introductionmentioning

confidence: 99%