@article{11cb1d92cf1b4d35a823447d563a42ec,
title = "Conformation of cyclic peptides. Principle concepts and the design of selectivity and superactivity in bioactive sequences by 'spatial screening'",
abstract = "The description of small cyclic peptide conformations can be simplified by substitution of the peptide bond for an olefinic structure, which then is converted into a single bond (for the E configuration) or a pseudo-CH2-group (for Z olefins). The resulting cycloalkane conformations are related to the observed cyclic peptide structures. The individual conformation, however, is strongly influenced by the array of chirality in the peptide sequence. This can be used for a {"}spatial screening{"} of biologically active peptide sequences. The procedure is demonstrated on selective and highly active inhibitors for αvβ3 integrins with a strong potential for development into anticancer drugs.",
author = "H. Kessler and R. Gratias and G. Hessler and M. Gurrath and G. M{\"u}ller",
note = "Funding Information: It was shown that conformational constraints of peptide structures can induce conformations in an often predictable way (14). If the bioactive conformation is not known, the spatial orientation of pharmacophoric groups on a distinct backbone conformation can be systematically screened. The procedure involves a shift of one (or more) D-amino acid@) around a distinct scaffold. The functional groups of the sidechains and their neighborhood are retained but their spatial arrangement can be adjusted. If one of these conformations matches the bound conformation (i.e. the conformation at its biological receptor) superactivity can be expected. In addition, the constraints often prevent binding to related receptor subtypes resulting in higher selectivity. This procedure is applied to design a potent lead structure for an anticancer drug. Today efficient screening strategies are being developed, especially using substance libraries. They may result in new lead structures which have to be refined by medicinal chemistry strategies. However, often the oligomeric components are flexible and the spatial orientation of the pharmacophoric groups is not known. The technique presented here provides the next step in the direction to useful drugs. Acknowledgement.. Financial support by the Deutsche Forschungsgemeinschaft and the Fonh der Chemischen Industrie is gratehlly acknowledged. The RGD work is also supported by E. Merck AG, Darmstadt.",
year = "1996",
month = jun,
doi = "10.1351/pac199668061201",
language = "English",
volume = "68",
pages = "1201--1205",
journal = "Pure and Applied Chemistry",
issn = "0033-4545",
publisher = "Walter de Gruyter GmbH",
number = "6",
}