The development and application of a novel safety-catch linker for BOC-based assembly of libraries of cyclic peptides

Cyclic peptides are appealing targets in the drug-discovery process. Unfortunately, there currently exist no robust solid-phase strategies that allow the synthesis of large arrays of discrete cyclic peptides. Existing strategies are complicated, when synthesizing large libraries, by the extensive workup that is required to extract the cyclic product from the deprotection/cleavage mixture. To overcome this, we have developed a new safety-catch linker. The safety-catch concept described here involves the use of a protected catechol derivative in which one of the hydroxyls is masked with a benzyl group during peptide synthesis, thus making the linker deactivated to aminolysis. This masked derivative of the linker allows BOC solid-phase peptide assembly of the linear precursor. Prior to cyclization, the linker is activated and the linear peptide deprotected using conditions commonly employed (TFMSA), resulting in deprotected peptide attached to the activated form of the linker. Scavengers and deprotection adducts are removed by simple washing and filtration. Upon neutralization of the N-terminal amine, cyclization with concomitant cleavage from the resin yields the cyclic peptide in DMF solution. Workup is simple solvent removal. To exemplify this strategy, several cyclic peptides were synthesized targeted toward the somatostatin and integrin receptors. From this initial study and to show the strength of this method, we were able to synthesize a cyclic-peptide library containing over 400 members. This linker technology provides a new solid-phase avenue to access large arrays of cyclic peptides.

National Library – Service Centre for All Types of Libraries in Finland

Kristiina Hormia-Poutasen esitys Jerusalemissa Israelin kansalliskirjastossa 8.9.2011

National Library – Service Centre for All Types of Libraries in Finland

Kristiina Hormia-Poutasen esitys Jerusalemissa 8.9.2011

The Finnish National Digital Library: a national service is developed in collaboration with a network of libraries, archives and museums

Insight-lehden numerossa 26 (Maaliskuu 2013) julkaistu artikkeli.

Library of libraries: approach to synthetic combinatorial library design and screening of "pharmacophore" motifs.

Construction of synthetic combinatorial libraries is described that allows for the generation of a library of motifs rather than a library of compounds. Peptide libraries based on this strategy were synthesized and screened with model targets streptavidin and anti-beta-endorphin antibody. The screens resulted in observation of expected motifs providing evidence of the effectiveness of the suggested approach.

Memoirs of libraries: including a handbook of library economy.

Plates part colored; list of illustrations inaccurate.

Role of libraries in distance education : a SPEC kit /

"July 1996."

The care of books : an essay on the development of libraries and their fittings, from the earliest times to the end of the eighteenth century /

Includes bibliographical references.

Guide to the use of libraries; a manual for college and university students.

Mode of access: Internet.

Michigan bibliography. A partial catalogue of books, maps, manuscripts and miscellaneous materials relating to the resources, development and history of Michigan from earliest times to July 1, 1917; together with citation of libraries in which the materials may be consulted, and a complete analytical index by subject and author.

Lettered on cover: Michigan bibliography. Streeter ... Michigan historical publications, 1921.

The American library annual : including index to dates of current events; necrology of writers; bibliographies; statistics of book production; select lists of libraries; directories of publishers and booksellers; list of private collectors of books, etc.

Subtitle varies.