solid-phase synthetic route to multiple derivatives of a fundamental peptide unit固相合成路线的多个衍生品基本肽单位.pdfVIP

Molecules 2010, 15, 4961-4983; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Solid-Phase Synthetic Route to Multiple Derivatives of a Fundamental Peptide Unit William L. Scott 1,*, Ziniu Zhou 1, Paweł Zajdel 2, Maciej Pawłowski 2 and Martin J. O’Donnell 1,* 1 Department of Chemistry and Chemical Biology, Indiana University-Purdue University Indianapolis, 402 N. Blackford Street, Indianapolis, IN 46202, USA 2 Department of Medicinal Chemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Kraków, Poland * Authors to whom correspondence should be addressed; E-Mails: wscott@ (W.L.S.); modonnel@ (M.J.O.). Received: 7 June 2010; in revised form: 23 June 2010 / Accepted: 12 July 2010 / Published: 20 July 2010 Abstract: Amino acids are Nature’s combinatorial building blocks. When substituted on both the amino and carboxyl sides they become the basic scaffold present in all peptides and proteins. We report a solid-phase synthetic route to large combinatorial variations of this fundamental scaffold, extending the variety of substituted biomimetic molecules available to successfully implement the Distributed Drug Discovery (D3) project. In a single solid-phase sequence, compatible with basic amine substituents, three-point variation is performed at the amino acid α-carbon and the amino and carboxyl functionalities. Keywords: Distributed Drug Discovery (D3); fundamental peptide scaffold; biom