t-Butyl Esters of Amino Acids and Peptides and their Use in Peptide Synthesis1
01 Jul 1960-Journal of the American Chemical Society (American Chemical Society)-Vol. 82, Iss: 13, pp 3359-3363
About: This article is published in Journal of the American Chemical Society.The article was published on 1960-07-01. It has received 258 citations till now. The article focuses on the topics: Edman degradation & Chemical ligation.
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TL;DR: In this article, the authors show that 1-Hydroxy-benzotriazol and 1-hydroxy-acetyl carbodiimid-methode eignen sich als Zusatze bei der Dicyclohexylcarbodiimids-Methode zur Synthese von Peptiden, verhindern die N-Acyl-harnstoffbildung and fuhren in hoher Ausbeute.
Abstract: 1-Hydroxy-benzotriazol sowie verschiedene kernsubstituierte 1-Hydroxy-benzotriazole eignen sich als Zusatze bei der Dicyclohexylcarbodiimid-Methode zur Synthese von Peptiden. Ihr Einflus auf die Racemisierung bei Peptidsynthesen wurde unter Anwendung des gaschromatographischen Racemisierungstests von Weygand u. Mitarbb.2) untersucht. Die neuen Zusatze senken die Racemisierung, verhindern die N-Acyl-harnstoffbildung und fuhren in hoher Ausbeute zu sehr reinen Peptiden.
1,475 citations
TL;DR: Albert Isidro-Llobet, Mercedes Alvarez,* and Fernando Albericio* Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac 10, 08028 Barcelona, Spain this paper.
Abstract: Albert Isidro-Llobet, Mercedes Alvarez,* and Fernando Albericio* Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac 10, 08028 Barcelona, Spain; CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Barcelona Science Park, Baldiri Reixac 10, 08028 Barcelona, Spain; Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain; and Department of Organic Chemistry, University of Barcelona, Marti i Franques 1, 08028 Barcelona, Spain Received April 28, 2008
646 citations
TL;DR: The number of synthetic peptides entering clinical trials has grown continuously over the last decade, and recent advances in the Fmoc SPPS technology are a response to the growing demand from medicinal chemistry and pharmacology.
Abstract: Today, Fmoc SPPS is the method of choice for peptide synthesis. Very-high-quality Fmoc building blocks are available at low cost because of the economies of scale arising from current multiton production of therapeutic peptides by Fmoc SPPS. Many modified derivatives are commercially available as Fmoc building blocks, making synthetic access to a broad range of peptide derivatives straightforward. The number of synthetic peptides entering clinical trials has grown continuously over the last decade, and recent advances in the Fmoc SPPS technology are a response to the growing demand from medicinal chemistry and pharmacology. Improvements are being continually reported for peptide quality, synthesis time and novel synthetic targets. Topical peptide research has contributed to a continuous improvement and expansion of Fmoc SPPS applications.
435 citations
176 citations
TL;DR: This review concentrates on the application of SPPS by Fmoc/t-Bu protecting-group strategy, which is most commonly used and represents innovative and potent methods for the development of novel peptide drug candidates that can be manufactured with optimized automated synthesis technologies.
Abstract: The great versatility and the inherent high affinities of peptides for their respective targets have led to tremendous progress for therapeutic applications in the last years. In order to increase the drugability of these frequently unstable and rapidly cleared molecules, chemical modifications are of great interest. Automated solid-phase peptide synthesis (SPPS) offers a suitable technology to produce chemically engineered peptides. This review concentrates on the application of SPPS by Fmoc/t-Bu protecting-group strategy, which is most commonly used. Critical issues and suggestions for the synthesis are covered. The development of automated methods from conventional to essentially improved microwave-assisted instruments is discussed. In order to improve pharmacokinetic properties of peptides, lipidation and PEGylation are described as covalent conjugation methods, which can be applied by a combination of automated and manual synthesis approaches. The synthesis and application of SPPS is described for neuropeptide Y receptor analogs as an example for bioactive hormones. The applied strategies represent innovative and potent methods for the development of novel peptide drug candidates that can be manufactured with optimized automated synthesis technologies.
175 citations